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1.
Br J Cancer ; 128(8): 1466-1477, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36759726

RESUMO

BACKGROUND: The clinical significance and immune correlation of CD103+ cells in prostate cancer (PCa) remain explored. METHODS: In total, 1080 patients with PCa underwent radical prostatectomy from three cohorts were enrolled for retrospective analysis. Tumour microarrays were constructed and fresh tumour samples were analysed by flow cytometry. RESULTS: High CD103+ cell infiltration correlated with reduced biochemical recurrence (BCR)-free survival in PCa. Adjuvant hormone therapy (HT) prolonged the BCR-free survival for high-risk node-negative diseases with CD103+ cell abundance. CD103+ cell infiltration correlated with less cytotoxic expression and increased infiltration of CD8+ and CD4+ T cells, M1 macrophages and mast cells in PCa. Intratumoral CD8+ T cell was the predominant source of CD103, and the CD103+ subset of CD8+ T cells was featured with high IL-10, PD-1 and CTLA-4 expression. Tumour-infiltrating CD103+ CD8+ T cells exerted anti-tumour function when treated with HT ex vivo. DISCUSSION: CD103+ cell infiltration predicted BCR-free survival and response to adjuvant HT in PCa. CD103+ cell infiltration correlated with an enriched but immune-evasive immune landscape. The study supported a model that CD103 expression conferred negative prognostic impact and immunosuppressive function to tumour-infiltrating CD8+ T cells, while the CD103+ CD8+ T cells exhibited a powerful anti-tumour immunity with response to HT.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias da Próstata , Humanos , Masculino , Cadeias alfa de Integrinas , Linfócitos do Interstício Tumoral , Prevalência , Prognóstico , Neoplasias da Próstata/terapia , Neoplasias da Próstata/metabolismo , Estudos Retrospectivos
2.
Mol Ther ; 30(3): 1054-1070, 2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35038580

RESUMO

Circular RNAs (circRNAs) play critical roles in different diseases. Exosomes are important intermediates of intercellular communication. While both have been widely reported in cancers, exosome-derived circRNAs are rarely studied. In this work, we identified the differently expressed circRNAs in bladder cancer (BCa) tissue and exosomes through high-throughput sequencing. RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays were used to investigate the interactions between specific circRNAs, microRNAs (miRNAs), and mRNAs. Wound-healing, Transwell, Cell Counting Kit-8 (CCK8), and colony-formation assays were used to study the biological roles in vitro. Metabolomics were used to explore the mechanism of how specific circRNAs influenced BCa cell behavior. Flow cytometry was used to study how specific circRNAs affected the function of CD8+ T cells in tumor microenvironments. We identified that exosome-derived hsa_circ_0085361 (circTRPS1) was correlated with aggressive phenotypes of BCa cells via sponging miR-141-3p. Metabolomics and RNA sequencing (RNA-seq) identified GLS1-mediated glutamine metabolism was involved in circTRPS1-mediated alterations. Exosomes derived from circTRPS1 knocked down BCa cells, prevented CD8+ T cells from exhaustion, and repressed the malignant phenotype of BCa cells. In conclusion, exosome-derived circTRPS1 from BCa cells can modulate the intracellular reactive oxygen species (ROS) balance and CD8+ T cell exhaustion via the circTRPS1/miR141-3p/GLS1 axis. Our work may provide a potential biomarker and therapeutic target for BCa.


Assuntos
Exossomos , MicroRNAs , Neoplasias , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Exossomos/genética , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias/genética , Fenótipo , RNA Circular/genética , Microambiente Tumoral/genética , Bexiga Urinária/metabolismo
3.
Cancer Sci ; 113(11): 3698-3709, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36018546

RESUMO

Recent studies identified Midkine (MDK) as playing a key role in immune regulation. In this study, we aimed to discover the clinical significance and translational relevance in prostate cancer (PCa). We retrospectively analyzed 759 PCa patients who underwent radical prostatectomy from Huashan Hospital, Fudan University (training cohort, n = 369) and Chinese Prostate Cancer Consortium (validation cohort, n = 390). A total of 325 PCa patients from The Cancer Genome Atlas (TCGA) database (external cohort) were analyzed for exploration. Immune landscape and antitumor immunity were assessed through immunohistochemistry and flow cytometry. Patient-derived explant culture system was applied for evaluating the targeting potential of MDK. We found that intratumoral MDK expression correlated with PCa progression, which indicated an unfavorable biochemical recurrence (BCR)-free survival for postoperative PCa patients. Addition of MDK expression to the postoperative risk assessment tool CAPRA-S could improve its prognostic value. Tumors with MDK abundance characterized the tumor-infiltrating CD8+ T cells with less cytotoxicity production and increased immune checkpoint expression, which were accompanied by enriched immunosuppressive contexture. Moreover, MDK inhibition could reactivate CD8+ T cell antitumor immunity. MDK mRNA expression negatively correlated with androgen receptor activity signature and positively associated with radiotherapy-related signature. In conclusion, intratumoral MDK expression could serve as an independent prognosticator for BCR in postoperative PCa patients. MDK expression impaired the antitumor function of CD8+ T cells through orchestrating an immunoevasive microenvironment, which could be reversed by MDK inhibition. Moreover, tumors with MDK enrichment possessed potential sensitivity to postoperative radiotherapy while resistance to adjuvant hormonal therapy of PCa. MDK could be considered as a potential therapeutic target for PCa.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias da Próstata , Masculino , Humanos , Midkina , Linfócitos T CD8-Positivos/metabolismo , Estudos Retrospectivos , Prognóstico , Neoplasias da Próstata/patologia , Microambiente Tumoral
4.
Minim Invasive Ther Allied Technol ; 29(6): 380-384, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31691623

RESUMO

Objectives: Double-lumen endotracheal tube (DLET) and one-lung ventilation (OLV) have been generally accepted as the classic anesthetic method in video-assisted thoracoscopic total thymectomy (VATT). However, there are still some disadvantages of DLET. Two-lung ventilation (TLV) with single-lumen endotracheal tube (SLET) is considered to be an alternative in VATT to avoid these disadvantages. This study evaluated the safety and feasibility of TLV in VATT by comparing it with OLV cases.Material and methods: We retrospectively screened 198 patients who received TLV unilateral thoracic incision VATT and 117 patients who received OLV unilateral thoracic incision VATT. Perioperative data were analyzed, including surgical variables, intraoperative hemodynamic parameters, and postoperative complications and hospital stay.Results: No significant differences with regard to operative time (p = .146), postoperative hospital stay (p = .553), complications (p = .254), hemodynamic parameters and pulse oxygen saturation (SpO2) were found between TLV group and OLV group. However, end-tidal CO2 (EtCO2) was higher in TLV group at 15 min (39.95 ± 5.03 vs 38.70 ± 4.57, p = .021) and 30 min (41.91 ± 5.50 vs 38.91 ± 4.51, p < .001) after initiation of the operation.Conclusions: It is safe and feasible to adopt TLV using SLET with CO2 insufflation artificial pneumothorax in unilateral thoracic incision VATT.


Assuntos
Ventilação Monopulmonar , Pneumotórax Artificial , Humanos , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida , Timectomia
6.
Int J Colorectal Dis ; 32(6): 897-905, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28176005

RESUMO

PURPOSE: Video-assisted thoracoscopic surgery (VATS) is widely used in thoracic surgery and increasingly applied to pulmonary metastasectomy. The purpose of this study was to identify prognostic factors of patients undergoing VATS pulmonary metastasectomy from colorectal cancer (CRC). METHODS: Between January 2005 and June 2015, a total of 154 patients underwent VATS pulmonary metastasectomy from CRC. Patient demographic data and characteristics of the primary tumor and pulmonary metastasis were analyzed to identify factors significantly correlated with prognosis. RESULTS: The median follow-up period after pulmonary resection was 37 months. The cumulative 5-year overall survival rate after VATS pulmonary metastasectomy from CRC was 71.3%. History of metastasis to other sites (p = 0.035), status of mediastinal lymph nodes (p < 0.001), and preoperative carcinoembryonic antigen (CEA) level (p = 0.013) were identified as independent prognostic factors. Subgroup analysis with a combination of these three independent prognostic factors revealed 5-year OS rates of 91.0, 70.0, 30.3, and 0.0% for patients with zero, one, two, and three risk factors, respectively. Other factors, such as sex, disease-free interval, T stage of primary tumor, and status of lymph node near the primary tumor, were not significantly associated with prognosis. CONCLUSION: VATS pulmonary metastasectomy is efficacious for patients with CRC pulmonary metastases. History of metastasis to other sites, status of mediastinal lymph nodes, and preoperative CEA level were identified as independent prognostic factors. The number of risk factors significantly influenced patient survival.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Metastasectomia , Cirurgia Torácica Vídeoassistida , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Análise de Sobrevida
7.
Epigenetics ; 18(1): 2178802, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36840946

RESUMO

Prostate cancer is the most prevalent type of cancer among men worldwide. The importance of circular RNA (circRNA) in prostate cancer and its connection to malignancy has been steadily recognized. circRNA expression was obtained by circRNA sequencing of prostate cancer. circRNA and its function were further analysed. The results were verified by qRT-PCR, RIP assay, FISH, RNA pulldown, WB, CCK-8, colony formation assay and wound-healing assay. BALB/c Nude mice were used for xenograft hosts. Low expression of circDHRS3 was assessed in prostate cancer. Overexpression of circDHRS3 inhibited prostate cancer growth and migration in vitro. Additionally, miR-421 was shown to be the downstream target of circDHRS3, as shown by fluorescence in situ hybridization and dual-luciferase experiments. The rescue assay results for the PC3 and Du145 cell lines demonstrated that circDHRS3 inhibits prostate cancer cell lines' ability to proliferate and metastasize by modulating MEIS2 expression through the circDHRS3/miR-421/MEIS2 axis. In vivo investigations confirmed that the overexpression of circDHRS3 could inhibit both the lung and bone metastasis of prostate cancer cells. circDHRS3 has the potential to become a biomarker and a targeted therapeutic site for prostate cancer, particularly in the malignant stage. Our study indicates that circDHRS3 inhibits prostate cancer cell proliferation and metastasis through the circDHRS3/miR-421/MEIS2 axis.


Assuntos
Proteínas de Homeodomínio , MicroRNAs , Neoplasias da Próstata , RNA Circular , Fatores de Transcrição , Animais , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Hibridização in Situ Fluorescente , Camundongos Nus , MicroRNAs/genética , Neoplasias da Próstata/genética , RNA Circular/genética , Fatores de Transcrição/genética , Oxirredutases do Álcool
8.
Front Nutr ; 10: 992608, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38188874

RESUMO

Background: The influences of blood lipids and lipid-regulatory medications on the risk of bladder cancer have long been suspected, and previous findings remain controversial. We aimed to assess the causality between blood lipids or lipid-regulatory medications and bladder cancer susceptibility by means of a comprehensive Mendelian Randomization (MR) study. Methods: Genetic proxies from genome-wide association studies (GWAS) of four blood lipid traits and lipid-lowering variants in genes encoding the targets of lipid-regulatory medications were employed. The largest ever GWAS data of blood lipids and bladder cancer involving up to 440,546 and 205,771 individuals of European ancestry were extracted from UK Biobank and FinnGen Project Round 6, respectively. A two-sample bidirectional MR study was performed using the inverse variance weighted as the main method. The heterogeneity, horizontal pleiotropy, MR Steiger, and leave-one-out analyses were also conducted as sensitivity tests. Results: There was indicative evidence that genetically predicted low-density lipoprotein cholesterol (LDL-C) affected bladder cancer susceptibility based on 146 single nucleotide polymorphisms (SNPs) with an odds ratio (OR) of 0.776 (95% confidence interval [CI] = 0.625-0.965, p = 0.022). However, this result became non-significant after two SNPs that possibly drove the effect were removed as demonstrated by leave-one-out analysis. The reversed MR analysis suggested that bladder cancer could not affect serum lipid levels. No causal relationship was found between the lipid-lowering effect of lipid-regulatory medications (fibrates, probucol, statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, and evinacumab) and the risk of bladder cancer. No heterogeneity or pleiotropy was found (all p > 0.05). Conclusion: This MR study revealed for the first time, using the most recent and comprehensive GWAS data to date, that genetically predicted total cholesterol (TC) and the lipid-lowering effect of lipid-regulatory medications had no causal association with bladder cancer susceptibility. We also verified claims from early studies that low-density lipoprotein cholesterol (HDL-C), LDL-C, and triglyceride (TG) are not related to bladder cancer susceptibility either. The current study indicated that lipid metabolism may not be as important in the tumorigenesis of bladder cancer as previously believed.

9.
Cell Death Dis ; 14(8): 525, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37582769

RESUMO

Metabolism vulnerability of cisplatin resistance in BCa cells remains to be discovered, which we applied integrated multi-omics analysis to elucidate the metabolism related regulation mechanism in bladder cancer (BCa) microenvironment. Integrated multi-omics analysis of metabolomics and proteomics revealed that MAT2A regulated methionine metabolism contributes to cisplatin resistance in BCa cells. We further validated MAT2A and cancer stem cell markers were up-regulated and circARHGAP10 was down-regulated through the regulation of MAT2A protein stability in cisplatin resistant BCa cells. circARHGAP10 formed a complex with MAT2A and TRIM25 to accelerate the degradation of MAT2A through ubiquitin-proteasome pathway. Knockdown of MAT2A through overexpression of circARHGAP10 and restriction of methionine up-take was sufficient to overcome cisplatin resistance in vivo in immuno-deficiency model but not in immuno-competent model. Tumor-infiltrating CD8+ T cells characterized an exhausted phenotype in tumors with low methionine. High expression of SLC7A6 in BCa negatively correlated with expression of CD8. Synergistic inhibition of MAT2A and SLC7A6 could overcome cisplatin resistance in immuno-competent model in vivo. Cisplatin resistant BCa cells rely on methionine for survival and stem cell renewal. circARHGAP10/TRIM25/MAT2A regulation pathway plays an important role in cisplatin resistant BCa cells while circARHGAP10 and SLC7A6 should be evaluated as one of the therapeutic target of cisplatin resistant BCa.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Metionina , Microambiente Tumoral , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Metionina/metabolismo , Proteômica , Metabolômica , Cisplatino/uso terapêutico , Células-Tronco Neoplásicas/patologia , RNA Circular/metabolismo , Ubiquitina/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitinação , Animais , Camundongos , Camundongos Nus , Camundongos Endogâmicos BALB C , Linfócitos T CD8-Positivos/imunologia
10.
Cell Death Discov ; 8(1): 68, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35173146

RESUMO

Clear cell renal cell carcinoma (ccRCC) is one of the most common urogenital tumors with high mortality. Circular RNA (circRNA), as an emerging endogenous RNA, has been proved to play a crucial role in the clear cell renal cell carcinoma (ccRCC) progression. In this study, we obtained circAFAP1 upregulated in ccRCC by high-sequencing and verified by qRT-PCR in several renal cancer cell lines. In situ hybridization (ISH) assays and Kaplan-Meier plot showed a higher level of circAFAP1 was linked to shorter overall survival. Moreover, CCK8, colony formation, and EdU experiments showed circAFAP1 promoted ccRCC growth while tube formation displayed circAFAP1 contributed to ccRCC angiogenesis. We predicted the downstream miR-374b-3p and VEGFA by bioinformatic analysis and validated further by qRT-PCR, RNA pull-down, RIP, and dual-luciferase. Downregulation miR-374b-3p or overexpression VEGFA could restore proliferation, vascular formation after circAFAP1 silencing. Consistently with the results in vitro, silencing circAFAP1 suppressed ccRCC growth in vivo. In conclusion, the circAFAP1/miR-374b-3p/VEGFA axis played a critical role in the progression and development of ccRCC which might be novel biological marks and therapeutical targets.

11.
Front Pharmacol ; 13: 932039, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910372

RESUMO

Our goal was to explore the bioactive constituents of Longsheyangquan (LSYQ) Decoction and elucidate its mechanisms on the treatment of bladder cancer (BCa). A total of 38 compounds were selected based on their pharmacokinetic properties in three large traditional Chinese medicine (TCM) databases. 654 putative targets of LSYQ Decoction were predicted using a structure-based, reverse-docking algorithm online, of which 343 overlapped with BCa-related protein-coding genes. The protein-protein interaction (PPI) network was constructed to perform module analysis for further Gene Ontology (GO) annotations and Kyoto Encyclopedia Genes and Genomes (KEGG) pathway enrichment analysis, which identified CDK2, EGFR, MMP9 and PTGS2 as hub targets. The TCM-compound-target network and compound-target-pathway network together revealed that quercetin, diosmetin, enhydrin and luteolin were the main components of LSYQ Decoction. Finally, molecular docking showed the affinity between the key compounds and the hub target proteins to verify the accuracy of drug target prediction in the first place. The present study deciphered the core components and targets of LSYQ Decoction on the treatment of BCa in a comprehensive systemic pharmacological manner.

12.
Cell Death Dis ; 12(8): 719, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285193

RESUMO

Bladder cancer (BC) is known as a common and lethal urinary malignancy worldwide. Circular RNAs (circRNAs), an emerging non-coding RNA, participate in carcinogenesis process of several cancers including BC. In this study, high-throughput sequencing and RT-qPCR were applied to discover and validate abnormal high expression of circUBE2K in BC tissues. Fluorescence in situ hybridization (FISH) was used to detect hsa_circ_0009154 (circUBE2K) expression and subcellular localization in BC tissues. High circUBE2K predicted unfavorable prognoses in BCs, as well as correlated with clinical features. CCK8, transwell, EdU and wound healing assays demonstrated down-regulating circUBE2K decreased BC cell phenotype as proliferation, invasion, and migration, respectively. Further studies showed that circUBE2K promoted BC progression via sponging miR-516b-5p and enhancing ARHGAP5 expression through regulating RhoA activity. Dual-luciferase reporter, FISH and RNA pulldown assays were employed to verify the relationships among circUBE2K/miR-516b-5p/ARHGAP5/RhoA axis. Down-regulating miR-516b-5p or overexpressing ARHGAP5 restored RhoA activity mediated BC cell properties after silencing circUBE2K. Subcutaneous xenograft and metastasis model identified circUBE2K significantly increased BC cell metastasis and proliferation in-vivo. Taken together, we found that circUBE2K is a tumor-promoting circRNA in BC that functions as a ceRNA to regulate ARHGAP5 expression via sponging miR-516b-5p.


Assuntos
Proteínas Ativadoras de GTPase/metabolismo , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , MicroRNAs/metabolismo , RNA Circular/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Proteína rhoA de Ligação ao GTP/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo/genética , Transição Epitelial-Mesenquimal , Inativação Gênica , Humanos , MicroRNAs/genética , Invasividade Neoplásica , Metástase Neoplásica , Fenótipo , Fosforilação , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Circular/genética , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Carga Tumoral , Regulação para Cima/genética
13.
Cell Death Dis ; 12(8): 778, 2021 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-34365465

RESUMO

Circular RNAs (circRNAs) drive several cellular processes including proliferation, survival, and differentiation. Here, we identified a circRNA hsa_circ_0007813, whose expression was upregulated in bladder cancer. High hsa_circ_0007813 expression was associated with larger tumor size, higher primary tumor T stage, and higher pathologic grade. Survival analysis showed that patients with high hsa_circ_0007813 expression levels had a poorer prognosis. Based on these findings from clinical tissue samples and cell lines, we assumed that hsa_circ_0007813 functioned a vital role in bladder cancer progression. Next, functional experiments revealed that knockdown of hsa_circ_0007813 inhibited proliferation, migration, and invasiveness of bladder cancer cells both in vitro and in vivo. Through extensive bioinformatic prediction and RNA pull-down assays, we identified hsa-miR-361-3p as a competing endogenous RNA of hsa_circ_0007813. Further bioinformatic studies narrowed targets to 35 possible downstream genes. We then found that knockdown of hsa_circ_0007813 led to altered cell autophagy, bringing our attention to IGF2R, one of the possible downstream genes. IGF2R was also known as cation-independent mannose-6-phosphate receptor (CI-M6PR), was discovered to participate in both autophagy and tumor biology. Regarding autophagy has a dominant role in the survival of tumor cells overcoming cellular stress and correlates with tumor progression, investigations were made to prove that hsa_circ_0007813 could regulate IGF2R expression via hsa-miR-361-3p sponging. The potential of hsa_circ_0007813 in regulating IGF2R expression explained its influence on cell behavior and clinical outcomes. Collectively, our data could offer new insight into the biology of circRNA in bladder cancer.


Assuntos
Autofagia/genética , Progressão da Doença , MicroRNAs/metabolismo , RNA Circular/metabolismo , Receptor IGF Tipo 2/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Animais , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Células HEK293 , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica , Fagossomos/metabolismo , Prognóstico , RNA Circular/genética , RNA Interferente Pequeno/metabolismo
14.
Mol Ther Nucleic Acids ; 23: 872-886, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33614236

RESUMO

Bladder cancer is a severe cancer with high mortality because of invasion and metastasis. Growing evidence has revealed that circular RNAs play critical roles in biological function, which is closely connected to proliferation and invasion of bladder cancer. In our study, we employed qRT-PCR, RNA fluorescence in situ hybridization (FISH), 5-ethynyl-2'-deoxyuridine (EdU), CCK-8, Transwell assays, luciferase reporter assays, xenografts, and live imaging to detect the roles of circular RNA binding protein with multiple splicing (circRBPMS) in bladder cancer (BC). Bioinformatics analysis and WB were performed to investigate the regulatory mechanism. Expression profile analysis of circular RNAs (circRNAs) in BC revealed that circRBPMS was significantly downregulated. Low circRBPMS expression correlates with aggressive BC phenotypes, whereas upregulation of circRBPMS suppresses BC cell proliferation and metastasis by directly targeting the miR-330-3p/ retinoic acid induced 2 (RAI2) axis. miR-330-3p upregulation or silencing of RAI2 restored BC cell proliferation, invasion, and migration following overexpression of circRBPMS. RAI2 silencing reversed miR-330-3p-induced cell invasion and migration as well as growth inhibition in vitro. Moreover, through bioinformatic analysis of the downstream target of RAI2 in the TCGA database, we identified and validated the biological role of circRBPMS through the RAI2-mediated ERK and epithelial-mesenchymal transition (EMT) pathways. We summarize the circRBPMS/miR-330-3p/RAI2 axis, where circRBPMS acts as a tumor suppressor, and provide a potential biomarker and therapeutic target for BC.

15.
Front Cell Dev Biol ; 9: 657219, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307347

RESUMO

Bladder cancer (BCa) is a common lethal urinary malignancy worldwide. The role of ARHGAP family genes in BCa and its association with immuno-microenvironment remain largely unknown. ARHGAP family expression and immune infiltration in BCa were analyzed by bioinformatics analysis. Then, we investigated cell proliferation, invasion, and migration in vivo and in vitro of the ARHGAP family. Furthermore, atomic force microscopy (AFM) was employed in measuring cellular mechanical properties of BCa cells. The results demonstrated that ARHGAP family genes correlate with a tumor-promoting microenvironment with a lower Th1/Th2 cell ratio, higher DC cell infiltration, higher Treg cell infiltration, and T-cell exhaustion phenotype. Silencing ARHGAP5, ARHGAP17, and ARHGAP24 suppressed BCa cell proliferation, migration, and metastasis. Knocking down of ARHGAPs in T24 cells caused a relatively higher Young's modulus and lower adhesive force and cell height. Taken together, ARHGAP family genes promote BCa progressing through establishing a tumor-promoting microenvironment and promoting cancer progression.

16.
Front Genet ; 11: 566918, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33424916

RESUMO

BACKGROUND: Bladder carcinoma (BC) is one of the most prevalent and malignant tumors. Multiple gene signatures based on BC metabolism, especially regarding glycolysis, remain unclear. Thus, we developed a glycolysis-related gene signature to be used for BC prognosis prediction. METHODS: Transcriptomic and clinical data were divided into a training set and a validation set after they were downloaded and analyzed from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Gene-set enrichment analysis (GSEA) and differential analysis were used to screen differentially expressed genes (DEGs), while univariate Cox regression and lasso-penalized Cox regression were employed for signature establishment. To evaluate the prognostic power of the signature, receiver operating characteristic (ROC) curve and Kaplan-Meier (KM) survival analysis were also used. Additionally, we developed a nomogram to predict patients' survival chances using the identified prognostic gene signature. Further, gene mutation and protein expression, as well as the independence of signature genes, were also analyzed. Finally, we also performed qPCR and western blot to detect the expression and potential pathways of signature genes in BC samples. RESULTS: Ten genes were selected for signature construction among 71 DEGs, including nine risk genes and one protection gene. KM survival analysis revealed that the high-risk group had poor survival and the low-risk group had increased survival. ROC curve analysis and the nomogram validated the accurate prediction of survival using a gene signature composed of 10 glycolysis-related genes. Western blot and qPCR analysis demonstrated that the expression trend of signature genes was basically consistent with previous results. These 10 glycolysis-related genes were independent and suitable for a signature. CONCLUSION: Our current study indicated that we successfully built and validated a novel 10-gene glycolysis-related signature for BC prognosis.

17.
Rev. psicol. deport ; 32(2): 186-195, Jun 20, 2023. tab, ilus
Artigo em Inglês | IBECS (Espanha) | ID: ibc-225178

RESUMO

This research study describes a modeling analysis of the correlation between children's language and thinking from the psychological perspective. This research study used specific questions related to the variables based on the primary data analysis for gathering the data. The data collected from almost 100 plus participants included children of school and colleges. The data collected from specific questions for measuring the data used IBM SPSS software to generate different informative numerical results that present the modeling correlation between dependent and independent variables. The children's language and thinking are the independent variables, and psychological perspective includes biological perspective, social perspective, developmental psychological perspective, and mental & health psychological perspective. These are all considered dependent variables. The descriptive statistical analysis, correlation coefficient, regression analysis, one-way ANOVA test analysis, variance ratio analysis, factor analysis, and principal components analysis between one variable and another variable. According to the comprehensive research study, the result found that children's language and thinking show a positive and significant correlation. The social perspective also shows a significant effect on children's language and thinking the mental health also plays an essential role in children's language.(AU)


Assuntos
Humanos , Masculino , Feminino , Criança , Psicologia da Criança , Saúde da Criança , Idioma , Pensamento , Desenvolvimento Infantil , Psicologia do Desenvolvimento
18.
J Thorac Dis ; 10(4): 2186-2195, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29850122

RESUMO

BACKGROUND: Uniport video-assisted thoracoscopic surgery (VATS) has emerged as a less invasive approach for the treatment of non-small cell lung cancer (NSCLC). However, whether uniport VATS has more potential advantages over multiport VATS remains controversial. This meta-analysis aimed to compare the perioperative efficacy of uniport and multiport VATS for T1-3N0M0 NSCLC. METHODS: An electronic and manual search of literature published before 1st October 2017 was conducted using PubMed, Embase, Web of Science, and the Wiley Online library. The effective values of dichotomous variables or continuous variables were estimated by odds ratios (OR) or by standardized mean differences (SMD) with 95% confidence intervals (CIs) respectively. RESULTS: Eleven relevant observational studies were included for meta-analysis. Results demonstrated that patients in the uniport group had a significant reduction in the duration of postoperative drainage (uniport: 4.39±2.48 vs. multiport: 4.99±3.24 days; P=0.003), bleeding volume (97.7±60.0 vs. 116.7±99.7 mL; P=0.006), length of hospital stay (6.3±2.4 vs. 7.0±3.6 days; P<0.001), VAS of postoperative pain (2.53±0.73 vs. 4.22±0.71, P=0.02) and in the overall rate of complications (14.5% vs. 17.5%; P=0.008). There were no significant differences between the two treatment groups with regards to mortality, operative time, the number of dissected lymph nodes or the conversion rate. CONCLUSIONS: Uniport VATS might have represent a preferable option for the treatment of T1-3N0M0 NSCLC, due to its superior perioperative efficacy.

20.
Onco Targets Ther ; 10: 2885-2892, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28652770

RESUMO

BACKGROUND: Stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy (SABR) has been reported to be a comparable alternative therapy to surgery for patients with T1-3N0M0 non-small cell lung cancer (NSCLC). However, it has not been clarified whether SBRT/SABR is as effective as surgery. We conducted this study to compare the efficacy of SBRT/SABR and surgery in the treatment of T1-3N0M0 NSCLC. MATERIALS AND METHODS: An electronic and a manual search of the literature was conducted in PubMed, Embase, and the Wiley Online Library in all published data before January 1, 2017. The pooled data included overall survival (OS), recurrence-free survival (RFS), and locoregional/distant recurrence rate. Hazard ratio (HR) of OS (SBRT/SABR vs surgery) was used as the measure of differential effects. RESULTS: Fifteen studies, including 7,810 patients with T1-3N0M0 NSCLC, 2,986 patients in the SBRT/SABR group, and 4,824 patients in the surgery group, were pooled for the meta-analysis. Results showed that patients with SBRT/SABR had a significantly worse 5-year survival rate (HR =1.40; 95% confidence interval [CI]: 1.21, 1.61; P<0.01), and RFS rate (HR =1.84; 95% CI: 1.26, 2.68; P=0.002). Meanwhile, the locoregional recurrence rate (HR =1.17; 95% CI: 0.68, 1.98; P=0.57), and distant recurrence rate (HR =1.36; 95% CI: 0.77, 2.39; P=0.29) were also lower in the surgery group although results were not statistically significant. In subgroup analyses, SBRT/SABR had a significantly lower rate of 5-year survival (HR =1.46; 95% CI: 1.03, 2.06; P=0.03) compared with lobectomy. Similarly, significant differences of OS exist in comparisons of SBRT/SABR versus sublobectomy (HR =1.40; 95% CI: 1.09, 1.80; P=0.008), and wedge resection (HR =1.48; 95% CI: 1.01, 2.16; P=0.04). CONCLUSION: Surgery, both lobectomy and sublobectomy, might be superior to SBRT/SABR with regard to survival of patients with T1-3N0M0 NSCLC. Patients with T1-3N0M0 NSCLC should preferably be treated surgically prior to SBRT/SABR.

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