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1.
Dis Markers ; 2023: 5025868, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36726845

RESUMO

Esophageal cancer (ESCA), as a common cancer worldwide, is a main cause of cancer-related mortality. Long noncoding RNAs (lncRNAs) have been shown in an increasing number of studies to be capable of playing an important regulatory function in human malignancies. Our study is aimed at delving into the prognostic value and potential function of lncRNA SSTR5-AS1 (SSTR5-AS1) in ESCA. The gene expression data of 182 ESCA samples from TCGA and 653 nontumor specimens from GTEx. The expressions of SSTR5-AS1 were analyzed. We investigated whether there was a correlation between the expression of SSTR5-AS1 and the clinical aspects of ESCA. In order to compare survival curves, the Kaplan-Meier method together with the log-rank test was utilized. The univariate and multivariate Cox regression models were used to analyze the data in order to determine the SSTR5-AS1 expression's significance as a prognostic factor in ESCA patients. In order to investigate the level of SSTR5-AS1 expression in ESCA cells, RT-PCR was utilized. CCK-8 trials served as a model for the loss-of-function tests. In this study, we found that the expressions of SSTR5-AS1 were increased in ESCA specimens compared with nontumor specimens. According to the ROC assays, high SSTR5-AS1 expression had an AUC value of 0.7812 (95% CI: 0.7406 to 0.8217) for ESCA. Patients who had a high level of SSTR5-AS1 expression had a lower overall survival rate than those who had a low level of SSTR5-AS1 expression. In addition, multivariate analysis suggested that SSTR5-AS1 was an independent predictor of overall survival for ESCA patients. Moreover, RT-PCR experiments indicated that SSTR5-AS1 expression was distinctly increased in three ESCA cells compared with HET1A cells. CCK-8 experiments indicated that silence of SSTR5-AS1 distinctly inhibited the proliferation of ESCA cells. Overall, ESCA patients with elevated SSTR5-AS1 had a worse chance of survival, suggesting it could be used as a prognostic and diagnostic biomarker for ESCA.


Assuntos
Neoplasias Esofágicas , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Sincalida/metabolismo , Prognóstico , Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica
2.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(1): 198-202, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36647667

RESUMO

Objective: To prepare cell membrane nanovesicles (NVs) derived from breast cancer cells, to explore their basic characteristics, tumor cell endocytosis, and in vivo distribution in a tumor-bearing mouse model, and to investigate their tumor targeting properties. Methods: 4T1 breast cancer cells were cultured in vitro. The cell membrane of 4T1 cells was isolated through ultracentrifugation and NVs were formulated with a liposome extruder. The size distribution of NVs was determined by way of dynamic light scattering, and the morphology properties of the NVs were examined with transmission electron microscope. The stability of NVs was analyzed by measuring the diameter changes of NVs submerged in phosphate-buffered saline (PBS). The biocompatibility of NVs was investigated by measuring the viability of dendritic cells treated with NVs at different concentrations (5, 10, 20, 50, and 100 mg·L -1) by CCK-8 assay. Fluorescence microscopy was used to analyze the cellular uptake of NVs by breast cancer cells. A mice model of breast cancer model was established with mice bearing subcutaneous xenograft of 4T1 cells. The mice were treated with Cy5.5-labeled NVs injected via the tail vein and the in vivo distribution of NVs was analyzed with an imaging system for small live animals. Results: The results showed that NVs derived from 4T1 breast cancer cells were successfully prepared. The NVs had a mean diameter of 123.2 nm and exhibited a hollow spherical structure under transmission electron microscope. No obvious change in the size of the NVs was observed after 7 days of incubation in PBS solution. CCK-8 assay results showed that the viability of dendritic cells treated with NVs at different concentrations was always higher than 90%. Fluorescence microscopic imaging showed that NVs could be efficiently internalized into breast cancer cells. in vivo biodistribution analysis revealed that breast cancer cell-derived NVs showed higher distribution in tumor tissue than the NVs prepared with normal cells did. Conclusion: We successfully prepared cell membrane NVs derived from 4T1 breast cancer cells. These NVs had efficient cellular uptake by breast cancer cells and sound tumor targeting properties.


Assuntos
Neoplasias da Mama , Sincalida , Humanos , Camundongos , Animais , Feminino , Distribuição Tecidual , Sincalida/metabolismo , Membrana Celular/metabolismo , Linhagem Celular Tumoral , Lipossomos , Neoplasias da Mama/metabolismo
3.
Zhonghua Zhong Liu Za Zhi ; 45(1): 50-55, 2023 Jan 23.
Artigo em Chinês | MEDLINE | ID: mdl-36709120

RESUMO

Objective: To observe the effects of exosomes derived from human umbilical cord mesenchymal stem cells on the proliferation and invasion of pancreatic cancer cells, and to analyze the contents of exosomes and explore the mechanisms affecting pancreatic cancer cells. Methods: Exosomes extracted from human umbilical cord mesenchymal stem cells were added to pancreatic cancer cells BxPC3, Panc-1 and mouse models of pancreatic cancer, respectively. The proliferative activity and invasion abilities of BxPC3 and Panc-1 cells were measured by cell counting kit-8 (CCK-8) and Transwell assays. The expressions of miRNAs in exosomes were detected by high-throughput sequencing. GO and KEGG were used to analyze the related functions and the main metabolic pathways of target genes with high expressions of miRNAs. Results: The results of CCK-8 cell proliferation assay showed that the absorbance of BxPC3 and Panc-1 cells in the hucMSCs-exo group was significantly higher than that in the control group [(4.68±0.09) vs. (3.68±0.01), P<0.05; (5.20±0.20) vs. (3.45±0.17), P<0.05]. Transwell test results showed that the number of invasion cells of BxPC3 and Panc-1 in hucMSCs-exo group was significantly higher than that in the control group (129.40±6.02) vs. (89.40±4.39), P<0.05; (134.40±7.02) vs. (97.00±6.08), P<0.05. In vivo experimental results showed that the tumor volume and weight in the exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-exo) group were significantly greater than that in the control group [(884.57±59.70) mm(3) vs. (695.09±57.81) mm(3), P<0.05; (0.94±0.21) g vs. (0.60±0.13) g, P<0.05]. High-throughput sequencing results showed that miR-148a-3p, miR-100-5p, miR-143-3p, miR-21-5p and miR-92a-3p were highly expressed. GO and KEGG analysis showed that the target genes of these miRNAs were mainly involved in the regulation of glucosaldehylation, and the main metabolic pathways were ascorbic acid and aldehyde acid metabolism, which were closely related to the development of pancreatic cancer. Conclusion: Exosomes derived from human umbilical cord mesenchymal stem cells can promote the growth of pancreatic cancer cells and the mechanism is related to miRNAs that are highly expressed in exosomes.


Assuntos
Carcinoma Ductal Pancreático , Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Neoplasias Pancreáticas , Camundongos , Animais , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Exossomos/genética , Sincalida/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Carcinoma Ductal Pancreático/genética , Células-Tronco Mesenquimais/metabolismo , Cordão Umbilical
4.
Horm Metab Res ; 55(2): 149-155, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36638810

RESUMO

Oxaliplatin is a member of the platinum group that is often used to treat glioma, a common type of malignant brain tumor, though it does not come with desirable and notable effects. This study attempted to investigate how ELK3 impacts the oxaliplatin resistance of glioma cells and its molecular mechanism. Bioinformatics analysis was employed to screen mRNAs with differential expression in glioma cells and predict the possible regulator downstream. We used qRT-PCR to detect the expression of ELK3 and RNASEH2A. Dual-luciferase and ChIP assays were adopted to reassure the regulatory relationship between the two. We also evaluated cell viability and sphere formation efficiency through CCK-8 and sphere formation assay and calculated the IC50 value by using CCK-8 assay. The expression of stemness-related proteins (ALDH1 and Nanog) was assessed through western blot. Glioma cells and tissues presented a significantly high expression of ELK3, the knock-down of which would reduce the cell viability, stemness and oxaliplatin resistance dramatically. Bioinformatics analysis predicted RNASEH2A to be the downstream regulator of ELK3. RNASEH2A was remarkably upregulated in glioma tissue and cells. The results from dual luciferase assay and ChIP experiment verified the binding relationship between RNASEH2A promoter region and ELK3. Then through rescue experiments, we confirmed that overexpression of RNASEH2A could compensate for the inhibition of glioma cell progression resulting from the knock-down of ELK3. ELK3 could promote stemness and oxaliplatin resistance of glioma cells by upregulating RNASEH2A, indicating that targeting ELK3/RNASEH2A axis may be a possible solution to overcome oxaliplatin resistance of glioma cells.


Assuntos
Glioma , MicroRNAs , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/farmacologia , Oxaliplatina/farmacologia , Sincalida/metabolismo , Sincalida/farmacologia , Linhagem Celular Tumoral , Glioma/tratamento farmacológico , Glioma/genética , Glioma/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-ets/metabolismo , Proteínas Proto-Oncogênicas c-ets/farmacologia
5.
J Zhejiang Univ Sci B ; 23(12): 989-1001, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36518052

RESUMO

OBJECTIVES: This research was performed to explore the effect of macrophage migration inhibitory factor (MIF) on the apoptosis of bone marrow mesenchymal stem cells (BMSCs) in ischemia and hypoxia environments. METHODS: The cell viability of BMSCs incubated under hypoxia/ischemia (H/I) conditions with or without pretreatment with MIF or triglycidyl isocyanurate (TGIC) was detected using cell counting kit-8 (CCK-8) analysis. Plasmids containing long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) or ß-catenin small interfering RNA (siRNA) were used to overexpress or downregulate the corresponding gene, and the p53 signaling pathway was activated by pretreatment with TGIC. The influences of MIF, overexpression of lncRNA MEG3, activation of the p53 signaling pathway, and silencing of ß-catenin on H/I-induced apoptosis of BMSCs were revealed by western blotting, flow cytometry, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining. RESULTS: From the results of CCK-8 assay, western blotting, and flow cytometry, pretreatment with MIF significantly decreased the H/I-induced apoptosis of BMSCs. This effect was inhibited when lncRNA MEG3 was overexpressed by plasmids containing MEG3. The p53 signaling pathway was activated by TGIC, and ß-catenin was silenced by siRNA. From western blot results, the expression levels of ß-catenin in the nucleus and phosphorylated p53 (p-p53) were downregulated and upregulated, respectively, when the lncRNA MEG3 was overexpressed. Through flow cytometry, MIF was also shown to significantly alleviate the increased reactive oxygen species (ROS) level of BMSCs caused by H/I. CONCLUSIONS: In summary, we conclude that MIF protected BMSCs from H/I-induced apoptosis by downregulating the lncRNA MEG3/p53 signaling pathway, activating the Wnt/ß-catenin signaling pathway, and decreasing ROS levels.


Assuntos
Fatores Inibidores da Migração de Macrófagos , Células-Tronco Mesenquimais , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fatores Inibidores da Migração de Macrófagos/genética , Fatores Inibidores da Migração de Macrófagos/metabolismo , beta Catenina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sincalida/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Apoptose , Via de Sinalização Wnt/genética , RNA Interferente Pequeno/metabolismo , Hipóxia/metabolismo , Isquemia , Células da Medula Óssea
6.
J Orthop Surg Res ; 17(1): 574, 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36585713

RESUMO

Rheumatoid arthritis (RA) is an autoimmune polyarthritis in which synovial fibroblasts (SF) play a major role in cartilage and bone destruction through tumorlike proliferation, migration, and invasion. Nesfatin-1, an 82-amino-acid-long peptide discovered by Oh-I in 2006, is derived from the precursor protein nucleobindin-2 (NUCB2). NUCB2/nesfatin-1 promotes cell proliferation, migration, and invasion in various tumors. We have previously shown that increased nesfatin-1 levels in the synovium may be associated with disease severity in patients with RA. However, the effect of NUCB2 on the tumorlike transformation of RASF has not yet been reported. The expression of NUCB2 mRNA in the synovium of RA and non-RA patients was further confirmed using three individual datasets from the NCBI GEO database. Gene set enrichment analysis (GSEA) was employed to explore the association between NUCB2 mRNA and RA-related gene signatures or signaling pathways in the GSE77298 dataset. Cell proliferation, migration, and invasion abilities were determined using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), wound healing, and transwell assays, respectively. The results showed that the levels of NUCB2 mRNA in the synovium were significantly elevated in patients with RA. Moreover, GSEA showed that high expression of NUCB2 mRNA was related to gene signatures, including those involved in the cell cycle, DNA replication, extracellular matrix-receptor interaction, and focal adhesion. Furthermore, the results of CCK-8 and EdU assays indicated that inhibition of NUCB2 markedly repressed RASF proliferation. Additionally, the results of wound healing and transwell assays demonstrated that inhibition of NUCB2 significantly suppressed the migratory and invasive abilities of RASFs. Our findings are the first to demonstrate that the inhibition of NUCB2 suppresses the proliferation, migration, and invasion of RASFs in vitro.


Assuntos
Artrite Reumatoide , Sincalida , Humanos , Sincalida/metabolismo , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Membrana Sinovial/metabolismo , Proliferação de Células/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fibroblastos/metabolismo , Movimento Celular/genética , Células Cultivadas
7.
Clin. transl. oncol. (Print) ; 24(11): 2136-2145, noviembre 2022.
Artigo em Inglês | IBECS | ID: ibc-210141

RESUMO

To investigate the subcellular localization of ANXA2 in breast cancer of different cell densities in humans and its relationship with the clinicopathological features of patients. To investigate the differences in ANXA2 subcellular localization in MDA-MB-231 cells of different cell densities. To compare the proliferation, invasion, and migration ability of MDA-MB-231 cells under different ANXA2 subcellular localization.MethodsImmunohistochemistry was applied to detect the subcellular localization of ANXA2 in tissue sections of 60 breast cancer patients, and the association with ANXA2 subcellular localization was verified in conjunction with cell density. To investigate the relationship between cell density and clinicopathological data of breast cancer patients. To establish high- and low-density models of MDA-MB-231 breast cancer cell lines and verify the subcellular localization of ANXA2 using immunofluorescence and observation under confocal microscopy. The proliferation, migration, and invasion ability of MDA-MB-231 cells under different subcellular localization of ANXA2 were detected and compared using CCK-8 assay and Transwell assay. After changing the subcellular localization of ANXA2 in high-density MDA-MB-231 cells with PY-60, changes in biological behaviors of the compared MDA-MB-231 cells were observed. Two different 4T1 cell lines with high and low densities were implanted subcutaneously in nude mice to observe the effects of different cell densities on tumor growth in nude mice.ResultsThe clinical data showed that breast cancer with high cell density had higher T stage and higher TNM stage, and the cell density was positively correlated with breast cancer mass size. ANXA2 was mainly localized to the cell membrane when the cell density of breast cancer cells was high and to the cytoplasm when the cell density was low. (AU)


Assuntos
Humanos , Animais , Anexina A2 , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , Sincalida/metabolismo , Movimento Celular , Camundongos
8.
Clin. transl. oncol. (Print) ; 24(11): 2166-2174, noviembre 2022.
Artigo em Inglês | IBECS | ID: ibc-210144

RESUMO

This study was designed to explore the role of COPZ1 in breast cancer as well as discuss its specific reaction mechanism.MethodsWith the help of RT-qPCR and western blot, the expression of BMI1 and COPZ1 were measured. Then, the proliferation, colony formation and apoptosis were evaluated by CCK-8, colony formation and TUNEL assays, separately. Luciferase reporter assay and ChIP were applied to assess the relative activity of COPZ1 promoter as well as its binding with BMI1. Moreover, western blot was utilized to measure the expression of proliferation-, apoptosis- and autophagy-related proteins.ResultsAccording to GEPIA2 database, COPZ1 was upregulated in breast cancer tissues and was associated with the poor prognosis (P = 0.03). Results obtained from RT-qPCR and western blot verified that COPZ1 expression was greatly increased at both mRNA and protein levels in breast cancer cells as compared to control cells (P < 0.05 or P < 0.001). COPZ1 knockdown inhibited the proliferation, induced the autophagy and promoted the apoptosis of breast cancer cells. HumanTFDB predicted the binding sites of BMI1 and COPZ1. The increased relative luciferase activity of COPZ1 promoter following BMI1 overexpression (P < 0.001) and the binding of BMI1 with COPZ1 promoter indicated that BMI1 could activate COPZ1. Further experiments suggested that the effects of COPZ1 knockdown on the proliferation, apoptosis and autophagy of breast cancer cells were reversed by BMI1 overexpression, implying that BMI1 promoted the proliferation and repressed the autophagy of breast cancer cells via activating COPZ1.ConclusionsTo sum up, BMI1 exhibited promotive effects on the malignant progression of breast cancer through the activation of COPZ1. These findings might offer a preliminary theoretical basis for COPZ1 participation in autophagy in breast cancer cells. (AU)


Assuntos
Humanos , Apoptose/genética , Autofagia , Proteínas , Neoplasias da Mama/patologia , Proliferação de Células , MicroRNAs/genética , Sincalida/metabolismo , Regulação Neoplásica da Expressão Gênica
9.
Oxid Med Cell Longev ; 2022: 8445093, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36285300

RESUMO

Background: It has been reported that signaling from the nerve growth factor (NGF) pathway associated with peripheral nerves is able to contribute to perineural invasion (PNI) of pancreatic cancer (PC). Nevertheless, the underlying mechanism by which NGF leads to PNI remained poorly understood. Methods: Western blotting was employed to determine NGF level in PC and paracarcinoma tissues and in PC cell lines as well as pancreatic ductal epithelial cells. MiaPaCa-2 and CFPAC-1 cells were treated with 100 ng/ml of NGF or the NGF inhibitor Tanezumab for 24 h, CCK-8 and Transwell assays were employed to test cell proliferation, invasion, and migration, respectively. TrkA expression was knocked down in MiaPaCa-2 and dorsal root ganglion (DRG) cells treated with NGF to determine its effect on the Warburg effect. To reveal that the NGF-TrkA signaling pathway was closely associated with PC PNI, in vitro neuroinvasion model was established by using MiaPaCa-2 cells via coculturing DRG cells in Matrigel. Further, exosomes were extracted from PC cells and identified by examining the levels of specific markers for exosomes. Then RT-qPCR was applied to test miR-21-5p level in tumor derived exosomal (TDE-miR-21-5p). RIP assay was performed to validate NGF and miR-21 binding ability in MiaPaCa-2 cells. Rescue experiments were performed by using coprocessing of Tanezumab and miR-21-5p mimic on MiaPaCa-2 cells, followed by coculture with DRG cells. Subsequently, we used a model of neuroinvasion in nude mice to assess the effect of NGF in vivo on tumor nerve invasion as well as on nociceptive transmission. Results: NGF level was preeminently higher in PC tissues and cell lines than in paracarcinoma tissues and normal pancreatic epithelial cell lines. NGF promoted MiaPaCa-2 and CFPAC-1 cell invasion and migration, while Tanezumab treatment showed the opposite results. Besides, NGF binding to TrkA receptors encouraged the intracellular Warburg effect in PC and DRG cells. TrkA blocking-up could restrain NGF induced PC cell migration and neural invasion. Mechanistically, NGF could upregulate TDE-miR-21-5p levels, and DRG cells took up TDE to activate the Warburg effect and stimulate nociceptor gene expression. miR-21-5p inhibitor could abolish the facilitative effect of NGF on PNI in MiaPaCa-2 cells. In vivo tumorigenesis experiments, Tanezumab markedly alleviated nerve invasion of PC cells as well as relieved nociceptive conduction in animal models. Conclusions: These findings displayed that NGF/TrkA encouraged the neuroinvasive potential of PC cells by activating the Warburg effect in DRG cells through upregulation of TDE-miR-21-5p expression.


Assuntos
MicroRNAs , Neoplasias Pancreáticas , Camundongos , Animais , Fator de Crescimento Neural/farmacologia , Fator de Crescimento Neural/genética , Invasividade Neoplásica , Camundongos Nus , Sincalida/genética , Sincalida/metabolismo , Diclorodifenildicloroetano , Linhagem Celular Tumoral , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proliferação de Células/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação Neoplásica da Expressão Gênica
10.
Oxid Med Cell Longev ; 2022: 5081439, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36275907

RESUMO

This study investigated the possibility of exosomes loaded with si-PDGFRß ability to suppress the progression of glioma. Common gliomas develop from neuroglial progenitor cells. Many variables affect the survival rate and occurrence of gliomas. Understanding oxidative stress processes and creating new, efficient treatments are crucial because oxidative stress is linked to the development of brain tumors. For this purpose, selected clinical samples were subjected to various tests like quantitative real-time PCR, Cignal Finder RTK signaling 7-pathway reporter array analysis, CCK-8 analysis, flow cytometry, and immunoblotting. Here, we demonstrated that PDGFRß expression was increased in glioma patients. Following that, cell-derived exosomes were extracted and collected and traced in vivo, and selected tissue samples were subjected to immunohistochemical analysis. The results indicated that the knockdown of PDGFRß (si-PDGFRß) inhibited the proliferation of glioma cells. Besides this, si-PDGFRß-loaded exosomes induced a similar antitumor effect in glioma cells. The anticancer effect of si-PDGFRß-loaded exosomes was mediated by the inactivation of the PI3K/Akt/EZH2 pathway. Finally, we verified that this exosome delivery system, si-PDGFRß-loaded exosomes, had robust targeting and no associated toxicity. In conclusion, the study confirmed that si-PDGFRß-loaded exosomes inhibit glioma progression via inactivating the PI3K/Akt/EZH2 signaling pathway.


Assuntos
Exossomos , Glioma , Humanos , Proliferação de Células , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Exossomos/metabolismo , Glioma/metabolismo , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Sincalida/metabolismo , Sincalida/farmacologia , Proteínas Proto-Oncogênicas c-sis/genética
11.
Biomed Environ Sci ; 35(9): 811-820, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36189996

RESUMO

Objective: High glucose (HG) can influence the osteogenic differentiation ability of periodontal ligament stem cells (PDLSCs). Human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-exo) have broad application prospects in tissue healing. The current study aimed to explore whether hUCMSC-exo could promote the osteogenic differentiation of hPDLSCs under HG conditions and the underlying mechanism. Methods: We used a 30 mmol/L glucose concentration to simulate HG conditions. CCK-8 assay was performed to evaluate the effect of hUCMSC-exo on the proliferation of hPDLSCs. Alkaline phosphatase (ALP) staining, ALP activity, and qRT-PCR were performed to evaluate the pro-osteogenic effect of hUCMSC-exo on hPDLSCs. Western blot analysis was conducted to evaluate the underlying mechanism. Results: The results of the CCK-8 assay, ALP staining, ALP activity, and qRT-PCR assay showed that hUCMSC-exo significantly promoted cell proliferation and osteogenic differentiation in a dose-dependent manner. The Western blot results revealed that hUCMSC-exo significantly increased the levels of p-PI3K and p-AKT in cells, and the effect was inhibited by LY294002 (PI3K inhibitor) or MK2206 (AKT inhibitor), respectively. Moreover, the increases in osteogenic indicators induced by hUCMSC-exo were significantly suppressed by LY294002 and MK2206. Conclusion: hUCMSC-exo promote the osteogenic differentiation of hPDLSCs under HG conditions through the PI3K/AKT signaling pathway.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Fosfatase Alcalina , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Exossomos/metabolismo , Glucose/metabolismo , Glucose/farmacologia , Humanos , Células-Tronco Mesenquimais/metabolismo , Osteogênese , Ligamento Periodontal/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Sincalida/metabolismo , Sincalida/farmacologia , Células-Tronco/metabolismo , Cordão Umbilical/metabolismo
12.
Comput Math Methods Med ; 2022: 2805645, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36238473

RESUMO

Objective: Optic nerve glioma (ONG) is a rare disease, defined as a WHO grade I tumor, which affects the visual pathway. The objective of this study was to investigate the expression of miR-223-3p in ONG as well as its function and regulation in ONG cell lines. Methods: qRT-PCR assays were used to measure miR-223-3p expression in ONG tissues and cell lines. After overexpression of miR-223-3p in Hs683 and WERI-Rb-1 cell lines, CCK-8 and EdU assays were performed to examine cell proliferation, and flow cytometry was used to assess apoptosis. Dual luciferase assays were utilized to identify the target binding to miR-223-3p and NLRP3. Rescue assays were carried out to investigate the regulatory mechanism of miR-223-3p acting through NLRP3. Nude mouse tumorigenesis assays were established to verify the effect of miR-223-3p on ONG growth. Results: miR-223-3p was weakly expressed in both ONG tissues and cell lines. miR-223-3p inhibited the proliferative ability of Hs683 and WERI-Rb-1 cell lines and promoted apoptosis. In addition, there was binding between miR-223-3p and NLRP3. Simultaneous overexpression of NLRP3 and miR-223-3p partially counteracted the role of miR-223-3p in the cell lines. Lastly, miR-223-3p inhibited ONG growth. Conclusion: miR-223-3p plays an inhibitory role in ONG development by regulating NLRP3 to inhibit the proliferation of ONG cells and promote apoptosis.


Assuntos
MicroRNAs , Glioma do Nervo Óptico , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sincalida/metabolismo
13.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(10): 1277-1287, 2022 Oct 15.
Artigo em Chinês | MEDLINE | ID: mdl-36310467

RESUMO

Objective: To explore the effect of Kaempferol on bone microvascular endothelial cells (BMECs) in glucocorticoid induced osteonecrosis of the femoral head (GIONFH) in vitro. Methods: BMECs were isolated from cancellous bone of femoral head or femoral neck donated voluntarily by patients with femoral neck fracture. BMECs were identified by von Willebrand factor and CD31 immunofluorescence staining and tube formation assay. The cell counting kit 8 (CCK-8) assay was used to screen the optimal concentration and the time point of dexamethasone (Dex) to inhibit the cell activity and the optimal concentration of Kaempferol to improve the inhibition of Dex. Then the BMECs were divided into 4 groups, namely, the cell group (group A), the cells treated with optimal concentration of Dex group (group B), the cells treated with optimal concentration of Dex+1 µmol/L Kaempferol group (group C), and the cells treated with optimal concentration of Dex+5 µmol/L Kaempferol group (group D). EdU assay, in vitro tube formation assay, TUNEL staining assay, Annexin Ⅴ/propidium iodide (PI) staining assay, Transwell migration assay, scratch healing assay, and Western blot assay were used to detect the effect of Kaempferol on the proliferation, tube formation, apoptosis, migration, and protein expression of BMECs treated with Dex. Results: The cultured cells were identified as BMECs. CCK-8 assay showed that the optimal concentration and the time point of Dex to inhibit cell activity was 300 µmol/L for 24 hours, and the optimal concentration of Kaempferol to improve the inhibitory activity of Dex was 1 µmol/L. EdU and tube formation assays showed that the cell proliferation rate, tube length, and number of branch points were significantly lower in groups B-D than in group A, and in groups B and D than in group C ( P<0.05). TUNEL and Annexin V/PI staining assays showed that the rates of TUNEL positive cells and apoptotic cells were significantly higher in groups B-D than in group A, and in groups B and D than in group C ( P<0.05). Scratch healing assay and Transwell migration assay showed that the scratch healing rate and the number of migration cells were significantly lower in groups B-D than in group A, and in groups B and D than in group C ( P<0.05). Western blot assay demonstrated that the relative expressions of Cleaved Caspase-3 and Bax proteins were significantly higher in groups B-D than in group A, and in groups B and D than in group C ( P<0.05); the relative expressions of matrix metalloproteinase 2, Cyclin D1, Cyclin E1, VEGFA, and Bcl2 proteins were significantly lower in groups B-D than in group A, and in groups B and D than in group C ( P<0.05). Conclusion: Kaempferol can alleviate the damage and dysfunction of BMECs in GIONFH.


Assuntos
Glucocorticoides , Osteonecrose , Humanos , Glucocorticoides/efeitos adversos , Células Endoteliais , Cabeça do Fêmur , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/farmacologia , Quempferóis/farmacologia , Quempferóis/metabolismo , Anexina A5/metabolismo , Anexina A5/farmacologia , Sincalida/metabolismo , Sincalida/farmacologia , Apoptose , Osteonecrose/induzido quimicamente , Osteonecrose/prevenção & controle
14.
Curr Med Sci ; 42(5): 974-980, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36245026

RESUMO

OBJECTIVE: The occurrence and development of inflammation are closely correlated to the polarization of macrophages. All-trans retinoic acid (ATRA) has been proven to promote the polarization of macrophages from M1 to M2, but this lacks an effective carrier to participate in the biological response. The present study aims to determine whether retinoic acid-incorporated glycol chitosan (RA-GC) nanoparticles can regulate macrophage polarization in Porphyromonas gingivalis-lipopolysaccharide (Pg-LPS)-induced inflammation. METHODS: Mouse 264.7 cell lines were treated with 1 µg/mL Pg-LPS to induce inflammation. After the effects of ATRA and RA-GC on the activity of macrophages were detected by CCK-8 assay, cells induced with Pg-LPS were assigned to the blank control group (GC) nanoparticles without ATRA, and experimental groups (GC nanoparticles loaded with different concentrations of ATRA: 1, 10 and 100 µg/mL). The effects of RA-GC on inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-10 and IL-12 in macrophages were detected by enzyme-linked immunosorbent assay (ELISA). Subsequently, the effects of GC nanoparticles loaded with/without ATRA on macrophage polarization in an inflammatory environment were detected by RT-PCR and Western blotting. RESULTS: The results revealed that RA-GC had no significant effect on macrophage activity. However, RA-GC could effectively inhibit the Pg-LPS-induced inflammatory factor expression in macrophages. Meanwhile, the experimental results confirmed that RA-GC could downregulate the expression of inducible nitric oxide synthase (iNOS) (a marker of M1 macrophages) and upregulate the expression of mannose receptor and Arginase-1 (a marker of M2 macrophages) in a dose-dependent manner. CONCLUSION: The present study confirms that RA-GC can promote the M2 polarization of macrophages in an inflammatory environment, and proposes this as a promising target for the clinical treatment of Pg-LPS-related diseases.


Assuntos
Lipopolissacarídeos , Nanopartículas , Camundongos , Animais , Lipopolissacarídeos/farmacologia , Porphyromonas gingivalis , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo II/farmacologia , Arginase , Fator de Necrose Tumoral alfa/metabolismo , Sincalida/metabolismo , Sincalida/farmacologia , Macrófagos/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Tretinoína/farmacologia , Citocinas/metabolismo , Interleucina-12
15.
Oxid Med Cell Longev ; 2022: 4320809, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246404

RESUMO

Background: Cancer-associated fibroblasts (CAFs) within the tumor microenvironment are key players in tumorigenesis and tumor development. Nevertheless, the regulatory mechanisms of CAFs on lung squamous cell carcinoma- (LUSC-) associated remain poorly elucidated. Methods: The microarray dataset GSE22874, containing 30 specimens of primary culture of normal fibroblasts (NFs) and 8 specimens of cancer-associated fibroblasts (CAFs) samples derived from LUSC, was retrieved from the Gene Expression Omnibus (GEO) database and then calculated by using the R language (limma package) to identify differentially expressed genes (DEGs). CAF-conditioned medium (CAF-CM) was collected and used to culture LUSC cells, followed by assessment of cell proliferation, apoptosis, and oxidative stress levels by using CCK-8, annexin V-FITC/PI double staining and ELISA assays. Subsequently, COL10A1 was knocked down in CAFs to assess the role of COL10A1 in CAF regulation of LUSC behavior. Bioinformatics online analysis and MeRIP were applied to predict and test the m6A modification of COL10A1 mRNA and the regulatory relationship with METTL3. Rescue experiments were next performed to explore the effects of METTL3 and COL10A1 in CAFs on LUSC cell proliferation, apoptosis, and oxidative stress. LUSC tumor cells with or without (COL10A1-silenced) CAFs were subcutaneously inoculated in nude mice to evaluate the effect of COL10A1 in CAFs on LUSC tumor growth. Results: Elevated expression of COL10A1 was found in LUSC-derived CAFs by GSE22874 dataset analysis. We discovered that COL10A1 and METTL3 was expressed in both LUSC cells and matched CAFs, while COL10A1 expression was prominently higher in CAFs than in LUSC cells. CAF-CM memorably encouraged LUSC cell proliferation and suppressed apoptosis-induced oxidative stress, which was reversed by interfering with COL10A1 expression in CAFs, suggesting that COL10A1 might be secreted by CAFs into the culture medium to exert its effects inside LUSC cells. Global m6A modification was decreased in METTL3 knocked down CAFs. M6A modification, expression levels, and stability of COL10A1 mRNA were impaired upon METTL3 knockdown in CAFs. Overexpression of COL10A1 in CAFs partially reversed the effect of METTL3 knockdown on the malignant behavior of LUSC cells. In vivo studies confirmed that CAFs accelerated LUSC tumor growth, and this effect was counteracted by COL10A1 silencing. Conclusions: COL10A1 secreted by CAFs could facilitate LUSC cell proliferation and repress apoptosis-induced oxidative stress, and the mechanism was due to elevated expression mediated by METTL3 promoting its mRNA m6A modification, thereby accelerating tumor growth.


Assuntos
Fibroblastos Associados a Câncer , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Animais , Apoptose/genética , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Colágeno Tipo X , Meios de Cultivo Condicionados/metabolismo , Fibroblastos/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/patologia , Metilação , Metiltransferases , Camundongos , Camundongos Nus , Estresse Oxidativo , RNA Mensageiro/metabolismo , Sincalida/metabolismo
16.
Dis Markers ; 2022: 5249910, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36277981

RESUMO

Objective: We aimed to investigate the role of ganoderic acid A (GAA) in glomerular mesangial cells (GMCs) under high glucose (HG). Methods: GMCs were pretreated with GAA and then cultured under HG condition for 24 h. Cell proliferation was measured by CCK-8 assay. The production of intracellular ROS was determined using DCFH-DA. The activities of SOD and CAT were measured using ELISA kits. The expressions of NOX2, NOX4, fibronectin (FN), collagen IV (col IV), p38, and p-p38 were detected by western blot. Results: GAA suppressed GMC proliferation in response to HG stimulation. GAA significantly attenuated HG-caused increase in ROS production and decreases in SOD and CAT activities in GMCs. In addition, the increased expressions of NOX2 and NOX4 and NOX activity in HG-induced GMCs were significantly decreased by GAA. Furthermore, GAA greatly inhibited the levels of FN and col IV in HG-stimulated GMCs. Mechanistic investigations showed that HG caused activation of p38 MAPK pathway, whereas the induction was mitigated by GAA. Notably, the specific agonist of p38 MAPK pathway (P79350) reversed the effects of GAA on GMCs. Conclusion: GAA protected GMCs from HG-induced oxidative stress and ECM production, which was mediated by the inhibition of the p38 MAPK pathway.


Assuntos
Fibronectinas , Células Mesangiais , Ratos , Animais , Células Mesangiais/metabolismo , Fibronectinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sincalida/metabolismo , Sincalida/farmacologia , Glucose/efeitos adversos , Glucose/metabolismo , Estresse Oxidativo , Matriz Extracelular , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Colágeno Tipo IV , Superóxido Dismutase/metabolismo , Células Cultivadas
17.
Cell Mol Biol Lett ; 27(1): 94, 2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36273140

RESUMO

BACKGROUND: Circular RNAs (circRNAs) appear to be important modulators in ovarian cancer. We aimed to explore the role and mechanism of circ_0025033 in ovarian cancer. METHODS: qRT-PCR was conducted to determine circ_0025033, hsa_miR-370-3p, and SLC1A5 mRNA expression. Functional experiments were conducted, including Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell, tube formation, xenograft tumor model assay, western blot analysis of protein levels, and analysis of glutamine metabolism using commercial kits. Their predicted interaction was confirmed using dual-luciferase reporter and RNA pull-down. RESULTS: circ_0025033 was upregulated in ovarian cancer; its knockdown induced proliferation, invasion, angiogenesis, glutamine metabolism, and apoptosis in vitro, and blocked tumor growth in vivo. circ_0025033 regulated ovarian cancer cellular behaviors via sponging hsa_miR-370-3p. In parallel, SLC1A5 might abolish the anti-ovarian cancer role of hsa_miR-370-3p. Furthermore, circ_0025033 affected SLC1A5 via regulating hsa_miR-370-3p. CONCLUSION: circ_0025033 might promote ovarian cancer progression via hsa_miR-370-3p/SLC1A5, providing an interesting insight into ovarian cancer tumorigenesis.


Assuntos
MicroRNAs , Neoplasias Ovarianas , RNA Circular , Feminino , Humanos , Sistema ASC de Transporte de Aminoácidos/genética , Sistema ASC de Transporte de Aminoácidos/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Glutamina/genética , Glutamina/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Antígenos de Histocompatibilidade Menor , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , RNA Mensageiro , Sincalida/genética , Sincalida/metabolismo
18.
Mol Med ; 28(1): 125, 2022 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-36273174

RESUMO

BACKGROUND: Oxidative stress-caused damage to the retinal pigment epithelium (RPE) underlies the onset and progression of age-related macular degeneration (AMD). Impaired mitochondrial biogenesis sensitizes RPE cells to mitochondrial dysfunction, energy insufficiency and death. Src-homology 2 domain-containing phosphatase (SHP)-1 is important in regulating immune responses and cell survival. However, its roles in cell survival are not always consistent. Until now, the effects of SHP-1 on RPE dysfunction, especially mitochondrial homeostasis, remain to be elucidated. We sought to clarify the effects of SHP-1 in RPE cells in response to atRAL-induced oxidative stress and determine the regulatory mechanisms involved. METHODS: In the all trans retinal (atRAL)-induced oxidative stress model, we used the vector of lentivirus to knockdown the expression of SHP-1 in ARPE-19 cells. CCK-8 assay, Annexin V/PI staining and JC-1 staining were utilized to determine the cell viability, cell apoptosis and mitochondrial membrane potential. We also used immunoprecipitation to examine the ubiquitination modification of stimulator of interferon genes (STING) and its interaction with SHP-1. The expression levels of mitochondrial marker, proteins related to mitochondrial biogenesis, and signaling molecules involved were examined by western blotting analysis. RESULTS: We found that SHP-1 knockdown predisposed RPE cells to apoptosis, aggravated mitochondrial damage, and repressed mitochondrial biogenesis after treatment with atRAL. Immunofluoresent staining and immunoprecipitation analysis confirmed that SHP-1 interacted with the endoplasmic reticulum-resident STING and suppressed K63-linked ubiquitination and activation of STING. Inhibition of STING with the specific antagonist H151 attenuated the effects of SHP-1 knockdown on mitochondrial biogenesis and oxidative damage. The adenosine monophosphate-activated protein kinase (AMPK) pathway acted as the crucial downstream target of STING and was involved in the regulatory processes. CONCLUSIONS: These findings suggest that SHP-1 knockdown potentiates STING overactivation and represses mitochondrial biogenesis and cell survival, at least in part by blocking the AMPK pathway in RPE cells. Therefore, restoring mitochondrial health by regulating SHP-1 in RPE cells may be a potential therapeutic strategy for degenerative retinal diseases including AMD.


Assuntos
Degeneração Macular , Mitocôndrias , Epitélio Pigmentado da Retina , Retinaldeído , Humanos , Monofosfato de Adenosina/metabolismo , Monofosfato de Adenosina/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Anexina A5/metabolismo , Anexina A5/farmacologia , Apoptose/genética , Interferons/genética , Interferons/metabolismo , Interferons/farmacologia , Degeneração Macular/genética , Degeneração Macular/metabolismo , Mitocôndrias/metabolismo , Biogênese de Organelas , Estresse Oxidativo , Monoéster Fosfórico Hidrolases/metabolismo , Monoéster Fosfórico Hidrolases/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Retinaldeído/metabolismo , Retinaldeído/farmacologia , Sincalida/metabolismo , Sincalida/farmacologia
19.
BMC Pharmacol Toxicol ; 23(1): 81, 2022 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-36273189

RESUMO

Vascular smooth muscle cell (VSMC) phenotypic modulation regulates the initiation and progression of intracranial aneurysm (IA). Dexmedetomidine (DEX) is suggested to play neuroprotective roles in patients with craniocerebral injury. Therefore, we investigated the biological functions of DEX and its mechanisms against IA formation and progression in the current study. The rat primary VSMCs were isolated from Sprague-Dawley rats. IA and superficial temporal artery (STA) tissue samples were obtained from patients with IA. Flow cytometry was conducted to identify the characteristics of isolated VSMCs. Hydrogen peroxide (H2O2) was used to mimic IA-like conditions in vitro. Cell viability was detected using CCK-8 assays. Wound healing and Transwell assays were performed to detect cell motility. ROS production was determined by immunofluorescence using DCFH-DA probes. Western blotting and RT-qPCR were carried out to measure gene expression levels. Inflammation responses were determined by measuring inflammatory cytokines. Immunohistochemistry staining was conducted to measure α2-adrenergic receptor levels in tissue samples. DEX alleviated the H2O2-induced cytotoxicity, attenuated the promoting effects of H2O2 on cell malignancy, and protected VSMCs against H2O2-induced oxidative damage and inflammation response. DEX regulated the GSK-3ß/MKP-1/NRF2 pathway via the α2AR. DEX alleviates the inflammatory responses and oxidative damage of VSMCs by regulating the GSK-3ß/MKP-1/NRF2 pathway via the α2AR in IA.


Assuntos
Dexmedetomidina , Aneurisma Intracraniano , Ratos , Animais , Glicogênio Sintase Quinase 3 beta/metabolismo , Glicogênio Sintase Quinase 3 beta/farmacologia , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Músculo Liso Vascular/metabolismo , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Peróxido de Hidrogênio , Aneurisma Intracraniano/tratamento farmacológico , Aneurisma Intracraniano/genética , Aneurisma Intracraniano/metabolismo , Ratos Sprague-Dawley , Sincalida/metabolismo , Sincalida/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo , Receptores Adrenérgicos alfa 2 , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Citocinas/metabolismo
20.
Front Immunol ; 13: 1022420, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36275722

RESUMO

Background: As a tumor type with high mortality and poor therapeutic effect, the pathogenesis of pancreatic cancer is still unclear. It is necessary to explore the significance of necroptosis in pancreatic cancer. Methods: Pancreatic cancer transcriptome data were obtained from the TCGA database, ICGC database, and GSE85916 in the GEO database. The TCGA cohort was set as a training cohort, while the ICGC and GSE85916 cohort were set as the validation cohorts. Single-cell sequencing data of pancreatic cancer were obtained from GSE154778 in the GEO database. The genes most associated with necroptosis were identified by weighted co-expression network analysis and single-cell sequencing analysis. COX regression and Lasso regression were performed for these genes, and the prognostic model was established. By calculating risk scores, pancreatic cancer patients could be divided into NCPTS_high and NCPTS_low groups, and survival analysis, immune infiltration analysis, and mutation analysis between groups were performed. Cell experiments including gene knockdown, CCK-8 assay, clone formation assay, transwell assay and wound healing assay were conducted to explore the role of the key gene EPS8 in pancreatic cancer. PCR assays on clinical samples were further used to verify EPS8 expression. Results: We constructed the necroptosis-related signature in pancreatic cancer using single-cell sequencing analysis and transcriptome analysis. The calculation formula of risk score was as follows: NCPTS = POLR3GL * (-0.404) + COL17A1 * (0.092) + DDIT4 * (0.007) + PDE4C * (0.057) + CLDN1 * 0.075 + HMGA2 * 0.056 + CENPF * 0.198 +EPS8 * 0.219. Through this signature, pancreatic cancer patients with different cohorts can be divided into NCPTS_high and NCPTS_low group, and the NCPTS_high group has a significantly poorer prognosis. Moreover, there were significant differences in immune infiltration level and mutation level between the two groups. Cell assays showed that in CAPAN-1 and PANC-1 cell lines, EPS8 knockdown significantly reduced the viability, clonogenesis, migration and invasion of pancreatic cancer cells. Clinical PCR assay of EPS8 expression showed that EPS8 expression was significantly up-regulated in pancreatic cancer (*P<0.05). Conclusion: Our study can provide a reference for the diagnosis, treatment and prognosis assessment of pancreatic cancer.


Assuntos
Necroptose , Neoplasias Pancreáticas , Humanos , Prognóstico , Necroptose/genética , Sincalida/genética , Sincalida/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Movimento Celular/genética , Neoplasias Pancreáticas/patologia , Perfilação da Expressão Gênica
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