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1.
FASEB J ; 37(3): e22824, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36809539

RESUMO

The present study investigated the effects of 2'-5' oligoadenylate synthetase-like (OASL) on the biological functions of stomach adenocarcinoma (STAD) cells and tumor formation in nude mice. The differential expression levels of OASL in the different cancer types from TCGA dataset were analyzed using gene expression profiling interactive analysis. Overall survival and the receiver operating characteristic were analyzed using the KM plotter and R, respectively. Furthermore, OASL expression and its effects on the biological functions of STAD cells were detected. The possible upstream transcription factors of OASL were predicted using JASPAR. The downstream signaling pathways of OASL were analyzed using GSEA. Tumor formation experiments were performed to evaluate the effect of OASL on tumor formation in nude mice. The results showed that OASL was highly expressed in STAD tissues and cell lines. OASL knockdown markedly inhibited cell viability, proliferation, migration, and invasion and accelerated STAD cell apoptosis. Conversely, OASL overexpression had the opposite effect on STAD cells. JASPAR analysis revealed that STAT1 is an upstream transcription factor of OASL. Furthermore, GSEA showed that OASL activated the mTORC1 signaling pathway in STAD. The protein expression levels of p-mTOR and p-RPS6KB1 were suppressed by OASL knockdown and promoted by OASL overexpression. The mTOR inhibitor, rapamycin, markedly reversed the effect of OASL overexpression on STAD cells. Additionally, OASL promoted tumor formation and increased tumor weight and volume in vivo. In conclusion, OASL knockdown suppressed the proliferation, migration, invasion, and tumor formation of STAD cells by inhibiting the mTOR signaling pathway.


Assuntos
2',5'-Oligoadenilato Sintetase , Adenocarcinoma , Neoplasias Gástricas , Animais , Camundongos , Adenocarcinoma/patologia , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos Nus , Transdução de Sinais , Neoplasias Gástricas/genética , Serina-Treonina Quinases TOR/metabolismo , 2',5'-Oligoadenilato Sintetase/genética
2.
Drug Resist Updat ; 68: 100936, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36764075

RESUMO

AIMS: Long non-coding RNAs (lncRNAs), as one of the components of exosomes derived from cancer-associated fibroblasts (CAFs), exhibit a crucial role in the pathogenesis and chemoresistance of gastric cancer (GC). Herein, we investigated the role and mechanism of a novel lncRNA disheveled binding antagonist of beta catenin3 antisense1 (DACT3-AS1) and its involvement in GC. METHODS: DACT3-AS1 was identified by RNA-sequencing and verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The functional role of DACT3-AS1 in GC was evaluated using in vitro and in vivo experiments including Transwell assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay, immunoblotting, and xenograft tumor mouse model. Dual-luciferase reporter assay was performed to assess the association between genes. RESULTS: DACT3-AS1 was downregulated and involved in poor prognosis of patients with GC. The results from both in vitro and in vivo experiments showed that DACT3-AS1 suppressed cell proliferation, migration, and invasion through targeting miR-181a-5p/sirtuin 1 (SIRT1) axis. Additionally, DACT3-AS1 was transmitted from CAFs to GC cells mainly via exosomes. Exosomal DACT3-AS1 alleviated xenograft tumor growth. DACT3-AS1 conferred sensitivity of cancer cells to oxaliplatin through SIRT1-mediated ferroptosis both in vitro and in vivo. CONCLUSIONS: CAFs-derived exosomal DACT3-AS1 is a suppressive regulator in malignant transformation and oxaliplatin resistance. DACT3-AS1 could be used for diagnosis and treatment of GC.


Assuntos
Fibroblastos Associados a Câncer , Ferroptose , MicroRNAs , Neoplasias Gástricas , Humanos , Camundongos , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Ferroptose/genética , Sirtuína 1/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Transformação Celular Neoplásica , Proliferação de Células , Linhagem Celular Tumoral , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
3.
Ecotoxicol Environ Saf ; 277: 116331, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38640801

RESUMO

Polystyrene nanoparticles are emerging as contaminants in freshwater environments, posing potential risks to amphibians exposed to extended periods of water contamination. Using tadpoles as a model, this study aimed to evaluate the toxicity of PS NPs. Pyrolysis-gas chromatography-tandem mass spectrometry (Py-GCMS) analysis revealed a concentration-dependent increase in polystyrene nanoparticles (PS NPs) levels in tadpoles with escalating exposure concentrations. Following exposure to 100 nm fluorescent microspheres, fluorescence was observed in the intestines and gills, peaking at 48 hours. Histopathological analysis identified degenerative necrosis and inflammation in the liver, along with atrophic necrosis of glomeruli and tubules in the kidneys. These results indicate a discernible impact of PS NPs on antioxidant levels, including reduced superoxide dismutase and catalase activities, elevated glutathione content, and increased malondialdehyde levels. Electron microscopy observations revealed the infiltration of PS NPs into Kupffer's cells and hepatocytes, leading to visible lesions such as nuclear condensation and mitochondrial disruption. The primary objective of this research was to elucidate the adverse effects of prolonged PS NPs exposure on amphibians.


Assuntos
Larva , Fígado , Nanopartículas , Estresse Oxidativo , Poliestirenos , Poluentes Químicos da Água , Animais , Poliestirenos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Nanopartículas/toxicidade , Fígado/efeitos dos fármacos , Fígado/patologia , Poluentes Químicos da Água/toxicidade , Larva/efeitos dos fármacos , Glutationa/metabolismo , Superóxido Dismutase/metabolismo , Malondialdeído/metabolismo , Catalase/metabolismo
4.
Int J Mol Sci ; 25(12)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38928167

RESUMO

The placenta is a crucial determinant of fetal survival, growth, and development. Deficiency in placental development directly causes intrauterine growth retardation (IUGR). IUGR can lead to fetal growth restriction and an increase in the mortality rate. The genetic mechanisms underlying IUGR development, however, remain unclear. In the present study, we integrated whole-genome DNA methylation and transcriptomic analyses to determine distinct gene expression patterns in various placental tissues to identify pivotal genes that are implicated with IUGR development. By performing RNA-sequencing analysis, 1487 differentially expressed genes (DEGs), with 737 upregulated and 750 downregulated genes, were identified in IUGR pigs (H_IUGR) compared with that in normal birth weight pigs (N_IUGR) (p < 0.05); furthermore, 77 miRNAs, 1331 lncRNAs, and 61 circRNAs were differentially expressed. The protein-protein interaction network analysis revealed that among these DEGs, the genes GNGT1, ANXA1, and CDC20 related to cellular developmental processes and blood vessel development were the key genes associated with the development of IUGR. A total of 495,870 differentially methylated regions were identified between the N_IUGR and H_IUGR groups, which included 25,053 differentially methylated genes (DMEs); moreover, the overall methylation level was higher in the H_IUGR group than in the N_IUGR group. Combined analysis showed an inverse correlation between methylation levels and gene expression. A total of 1375 genes involved in developmental processes, tissue development, and immune system regulation exhibited methylation differences in gene expression levels in the promoter regions and gene ontology regions. Five genes, namely, ANXA1, ADM, NRP2, SHH, and SMAD1, with high methylation levels were identified as potential contributors to IUGR development. These findings provide valuable insights that DNA methylation plays a crucial role in the epigenetic regulation of gene expression and mammalian development and that DNA-hypermethylated genes contribute to IUGR development in Rongchang pigs.


Assuntos
Metilação de DNA , Retardo do Crescimento Fetal , Placenta , Animais , Retardo do Crescimento Fetal/genética , Suínos , Feminino , Gravidez , Placenta/metabolismo , Perfilação da Expressão Gênica , Mapas de Interação de Proteínas/genética , Epigênese Genética , MicroRNAs/genética , Transcriptoma/genética , Redes Reguladoras de Genes
5.
EMBO Rep ; 22(11): e52707, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34472665

RESUMO

Genome-wide association studies (GWAS) have identified multiple gastric cancer risk loci and several protein-coding susceptibility genes. However, the role of long-noncoding RNAs (lncRNAs) transcribed from these risk loci in gastric cancer development and progression remains to be explored. Here, we functionally characterize a lncRNA, lncPSCA, as a novel tumor suppressor whose expression is fine-regulated by a gastric cancer risk-associated genetic variant. The rs2978980 T > G change in an intronic enhancer of lncPSCA interrupts binding of transcription factor RORA, which down-regulates lncPSCA expression in an allele-specific manner. LncPSCA interacts with DDX5 and promotes DDX5 degradation through ubiquitination. Increased expression of lncPSCA results in low levels of DDX5, less RNA polymerase II (Pol II) binding with DDX5 in the nucleus, thus activating transcription of multiple p53 signaling genes by Pol II. These findings highlight the importance of functionally annotating lncRNAs in GWAS risk loci and the great potential of modulating lncRNAs as innovative cancer therapy.


Assuntos
RNA Longo não Codificante , Neoplasias Gástricas , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Regulação Neoplásica da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/genética , Fatores de Transcrição/metabolismo
6.
Surg Endosc ; 37(10): 7729-7737, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37566117

RESUMO

BACKGROUND: The purpose of this research was to evaluate the safety and efficacy of a self-expandable metallic stent (SEMS) combined with iodine-125 (125I) seeds in the treatment of Bismuth type I or II malignant biliary obstruction (MBO). METHODS: The clinical data of 74 cases of MBO treated with percutaneous SEMS combined with 125I seeds (combination group) and 81 cases of MBO treated with SEMS implantation alone (control group) in our hospital from January 2015 to December 2019 were retrospectively analyzed. The short-term and long-term efficacy of the two groups were compared. Multivariate Cox regression analysis was used to analyze the factors affecting the surgical efficacy and survival rate. RESULTS: The liver blood test results of both groups improved at one week and one month post-stent insertion. No significant difference was established in the short-term efficacy or complications between the two groups (P = NS). Improved stent patency was observed in the combined group, 9.01 ± 4.38 months versus 6.79 ± 3.13 months, respectively (P < 0.001). Improved survival was also noted in the combined group 12.08 ± 5.38 months and 9.10 ± 4.16 months, respectively (P < 0.001). Univariate and multivariate analyses showed that the type of biliary stent and liver metastasis were independent factors affecting survival. CONCLUSION: The implementation of SEMS combined with 125I seeds resulted in significantly longer stent patency and survival times than that of SEMS implantation alone, which is thus worthy of clinical promotion and application.


Assuntos
Colestase , Stents Metálicos Autoexpansíveis , Humanos , Bismuto , Colestase/etiologia , Colestase/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Stents Metálicos Autoexpansíveis/efeitos adversos , Stents/efeitos adversos
7.
Vet Med (Praha) ; 68(10): 392-402, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38028206

RESUMO

Rongchang piglets were easily induced to cold stress and diarrhoea in the winter when raised in an open hog house. However, they also gradually recovered under mid-cold stress. Other studies have suggested gut microbiome might be involved in the host energy metabolism to relieve stress. To study how to adapt Rongchang piglets to cold stress by gut microbiome, thirty Rongchang piglets were randomly divided into a mild cold stress group and a control group for 30 consecutive days. The findings revealed that the piglets had low growth performance and a high diarrhoea rate and mortality rate during the first half of the cold treatment, but subsequently stabilised. The level of cortisol (COR) also displayed a similar trend. In the mild cold stress group, the relative abundance of Muribaculaceae significantly increased on day 15, and the predominant bacterial on day 30 was Lactobacillus sp. Our results indicated that the Rongchang piglet's production performance and health were impaired at the start of the mild cold stress. However, as time passed, the body could progressively adapt to the low temperature, and Lactobacillus sp. participated in this process. This study provides new insight into how to alleviate health damage caused by cold stress.

8.
Future Oncol ; 18(36): 4005-4015, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36382581

RESUMO

Aims: To determine the effectiveness and safety of sequential computed tomography-guided percutaneous microwave ablation (MWA) after transcatheter arterial chemoembolization (TACE) for hypovascular liver lesions <5 cm in size. Methods: The clinical data of 69 hypovascular hepatocellular carcinoma lesions <5 cm in 60 patients treated with TACE followed by MWA were retrospectively analyzed. Results: There was no significant difference in AFP levels among AFP-positive patients before and after TACE (p = 0.515), but levels were significantly lower 1 month after MWA than before MWA (p = 0.039). Compared with 1 month after TACE, the objective response rate (p < 0.001) and disease control rate (p = 0.004) were increased 1 month after MWA. Any adverse events were well tolerated, and the albumin bilirubin score did not deteriorate within 4 weeks. Conclusion: Sequential MWA after TACE was found to be safe and effective for treating hypovascular hepatocellular carcinoma for lesions <5 cm in size.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Micro-Ondas/efeitos adversos , Estudos Retrospectivos , alfa-Fetoproteínas , Quimioembolização Terapêutica/efeitos adversos , Terapia Combinada , Resultado do Tratamento
9.
BMC Pulm Med ; 22(1): 336, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064381

RESUMO

BACKGROUND: Direct localization of small and deep pulmonary nodules before thoracoscopic surgery using the hookwire or methylene blue techniques has been recently attempted for better surgical outcomes. In this study, we compare the outcomes of the above two techniques. METHODS: Two hundred and nineteen patients undergoing 135 hookwire and 151 methylene blue techniques in our University Hospital between July 2020 and January 2022 were compared for localization and hospitalization durations, and the complication risk. Other confounders included patients' age, gender, localization position, nodules location, count, diameter, and depth. RESULTS: After adjustment of all predictors, the methylene blue technique was associated with a significant 0.6-min (parameter estimate (PE) = -0.568, p value = 0.0173) and an 0.7-day shorter localization and hospitalization time (PE = -0.713, p value = < 0.0001) as compared to using the hookwire technique. The hookwire technique was significantly associated with 5 times the risk of developing a post-localization complication (Adjusted Odds Ratio (Adj OR) = 4.52, 95% CI 1.53-13.33) and 3.6 times the risk of developing a pneumothorax (Adj OR = 3.57, 95% CI 1.1-11.62) as compared to adopting the methylene blue technique. CONCLUSIONS: Compared to the hook wire technique, the methylene blue technique offers a shorter procedure and hospitalization stay, as well as a safer post-operative experience.


Assuntos
Neoplasias Pulmonares , Nódulo Pulmonar Solitário , Humanos , Tempo de Internação , Neoplasias Pulmonares/cirurgia , Azul de Metileno , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/cirurgia , Toracoscopia/efeitos adversos , Toracoscopia/métodos , Tomografia Computadorizada por Raios X/métodos
10.
Cancer Cell Int ; 20(1): 580, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33292253

RESUMO

BACKGROUND: Despite an enormous research effort, patients diagnosed with advanced colorectal cancer (CRC) still have low prognosis after surgical resection and chemotherapy. The major obstacle for CRC treatment is chemoresistance to front line anti-cancer drugs, such as 5-fluorouracil (5-FU) and oxaliplatin. However, the mechanism of chemoresistance to these drugs remains unclear. METHODS: Cell viability to 5-FU and oxaliplatin was measured by the CellTiter-Glo® 2.0 Cell Viability Assay. The endogenous REV7 protein in CRC cells was detected by western blotting. The translesion synthesis (TLS) events were measured by plasmid-based TLS efficiency assay. Cell apoptosis was evaluated by caspase3/7 activity assay. The in vivo tumor progression was analyzed by HT29 xenograft mice model. RESULTS: In this study, we found that expression of REV7, which is a key component of translesion synthesis (TLS) polymerase ζ (POL ζ), is significantly increased in both 5-FU and oxaliplatin resistant CRC cells. TLS efficiency analysis revealed that upregulated REV7 protein level results in enhanced TLS in response to 5-FU and oxaliplatin. Importantly, inhibition of REV7 by CRISPR/Cas9 knockout exhibited significant synergy with 5-FU and oxaliplatin in cell culture and murine xenograft model. CONCLUSION: These results suggest that combination of REV7 deficiency and 5-FU or oxaliplatin has strong inhibitory effects on CRC cells and identified REV7 as a promising target for chemoresistant CRC treatment.

11.
Cancer Cell Int ; 20: 505, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33071648

RESUMO

BACKGROUND: Cancer stem cells (CSCs) play an important role in tumor invasion and metastasis. CD44 is the most commonly used marker of CSCs, with the potential to act as a determinant against the invasion and migration of CSCs and as the key factor in epithelial-mesenchymal transition (EMT)-like changes that occur in colorectal cancer (CRC). Runt-related transcription factor-2 (RUNX2) is a mesenchymal stem marker for cancer that is involved in stem cell biology and tumorigenesis. However, whether RUNX2 is involved in CSC and in inducing EMT-like changes in CRC remains uncertain, warranting further investigation. METHODS: We evaluated the role of RUNX2 in the invasion and migration of CRC cells as a promoter of CD44-induced stem cell- and EMT-like modifications. For this purpose, western blotting was employed to analyze the expression of differential proteins in CRC cells. We conducted sphere formation, wound healing, and transwell assays to investigate the biological functions of RUNX2 in CRC cells. Cellular immunofluorescence and coimmunoprecipitation (co-IP) assays were performed to study the relationship between RUNX2 and BRG1. Real-time quantitative PCR (RT-qPCR) and immunohistochemistry (IHC) were performed to analyze the expressions of RUNX2, BRG1, and CD44 in the CRC tissues. RESULTS: We found that RUNX2 could markedly induce the CRC cell sphere-forming ability and EMT. Interestingly, the RUNX2-mediated EMT in CRC cell may be associated with the activation of CD44. Furthermore, RUNX2 was found to interact with BRG1 to promote the recruitment of RUNX2 to the CD44 promoter. CONCLUSIONS: Our cumulative findings suggest that RUNX2 and BRG1 can form a compact complex to regulate the transcription and expression of CD44, which has possible involvement in the invasion and migration of CRC cells.

12.
J Am Chem Soc ; 141(23): 9151-9154, 2019 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-31083943

RESUMO

A CoII18L6 hexameric metal-organic nanocapsule (MONC) has been prepared and characterized using biomimetic self-assembly as the synthetic methodology. Akin to the biological behavior of zinc-finger proteins' release, uptake, and electrophilic substitution of Zn2+ ions, the assembly of this novel MONC has been accomplished by employing three sequential processes: assembly of the framework, metal ion insertion, and metal exchange, resulting in the formation of the CoII18L6 hexameric MONC. In this work, inspired by the biological behavior of metalloproteins, rational control of multiple complex supramolecular self-assembly has been achieved.


Assuntos
Biomimética , Engenharia Química , Cobalto/química , Nanopartículas Metálicas/química , Modelos Moleculares , Estrutura Molecular
13.
Sensors (Basel) ; 19(7)2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30987407

RESUMO

Low-cost microelectro mechanical systems (MEMS)-based inertial measurement unit (IMU) measurements are usually affected by inaccurate scale factors, axis misalignments, and g-sensitivity errors. These errors may significantly influence the performance of visual-inertial methods. In this paper, we propose an online IMU self-calibration method for visual-inertial systems equipped with a low-cost inertial sensor. The goal of our method is to concurrently perform 3D pose estimation and online IMU calibration based on optimization methods in unknown environments without any external equipment. To achieve this goal, we firstly develop a novel preintegration method that can handle the IMU intrinsic parameters error propagation. Then, we frame IMU calibration problem into general factors so that we can easily integrate the factors into the current graph-based visual-inertial frameworks and jointly optimize the IMU intrinsic parameters as well as the system states in a big bundle. We evaluate the proposed method with a publicly available dataset. Experimental results verify that the proposed approach is able to accurately calibrate all the considered parameters in real time, leading to significant improvement of estimation precision of visual-inertial system (VINS) compared with the estimation results with offline precalibrated IMU measurements.

14.
Biosci Biotechnol Biochem ; 82(7): 1081-1089, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29658390

RESUMO

Sequence variation in a microRNA (miRNA) seed region can influence its biogenesis and effects on target mRNAs; however, in mammals, few seed region mutations leading to functional alterations have been reported to date. Here, we report the identification of a single nucleotide polymorphism (SNP) with functional consequence located in the seed region of porcine miR-378. In vitro analysis of this rs331295049 A17G SNP showed significantly up-regulated expression of the mature miR-378 (miR-378/G). In silico target prediction indicated that the SNP would modulate secondary structure and result in functional loss affecting >85% of the known target genes of the wild-type miR-378 (miR-378/A), and functional gain affecting >700 new target genes, and dual-luciferase reporter assay verified this result. This report of a SNP in the seed region of miR-378 leads to functional alteration and indicates the potential for substantive functional consequences to the molecular physiology of a mammalian organism.


Assuntos
MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Suínos/genética , Células 3T3-L1 , Animais , Simulação por Computador , Regulação para Baixo , Metabolismo Energético/genética , Feminino , Perfilação da Expressão Gênica , Genes Reporter , Células HEK293 , Humanos , Lipogênese/genética , Luciferases/genética , Camundongos , MicroRNAs/química , MicroRNAs/fisiologia , Músculo Esquelético/crescimento & desenvolvimento , Conformação de Ácido Nucleico , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima
15.
Tumour Biol ; 37(3): 2973-85, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26415732

RESUMO

MicroRNAs (miRNAs) as a class of small noncoding RNA molecules regulate the expression of targeted gene. The dysregulation of microRNAs is reported to be involved in carcinogenesis and tumor progression. Here, we identified miR-140-3p as a downregulated microRNA in most cancer tissues including lung cancer tissues, compared with their normal counterparts. MiR-140-3p was observed to perform its tumor suppressor function via its inhibition on cell growth, migration and invasion but its induction of cell apoptosis. Furthermore, the growth of non-small-cell lung cancer (NSCLC) cells in nude mouse models were suppressed by overexpression of miR-140-3p. ATP8A1 was demonstrated as a novel direct target of miR-140-3p using a luciferase assay. The increased level of intracellular ATP8A1 protein attenuated the inhibitor role of miR-140-3p in the growth and mobility of NSCLC cell. A regulation mechanism of miR-140-3p for the development and progression of NSCLC through downregulating the ATP8A1 expression was first discovered in the present study.


Assuntos
Adenosina Trifosfatases/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , MicroRNAs/fisiologia , Proteínas de Transferência de Fosfolipídeos/genética , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Invasividade Neoplásica
16.
BMC Complement Altern Med ; 16(1): 428, 2016 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-27806701

RESUMO

BACKGROUND: Yi Ai Fang (YAF), a traditional Chinese medicine (TCM) formula, has been identified to have anticancer activity in our previously studies. The present study aimed to explore the potential mechanism of YAF suppression of VM on colorectal cancer (CRC) in vitro and in vivo. METHODS: Cell viability was measured by CCK-8 assay. HIF-1α, E-cd(E-cadherin), Claudin-4, and VIM (Vimentin) expressions level in vitro were evaluated by Western blot or RT-PCR. In addition, Human CRC HCT-116 cells were implanted in BALB/c nude mice; mice with xenografted tumors were randomly administrated vehicle (control), 8, 16, or 32 mg/mL YAF, or 1 mg/mL fluorouracil (5-FU). HIF-1α, E-cd, Claudin-4, and VIM expression in these tumors were determined by IHC. RESULTS: YAF effectively inhibited the growth and the formation of vasculogenic mimicry (VM) of CRC cells in a dose-dependent trend. YAF restrained the formation of vasculogenic mimicry(VM) through HIF-1α/EMT pathway in CRC. YAF suppressed VM was triggered by activation of E-cd and Claudin-4,which are characteristics of endothelial cells,and inhibition of HIF-1α and VIM in vitro. In vivo data showed that YAF remarkably inhibited growth of the xenografted tumors. The YAF-treated tumor samples were analyzed by IHC for levels of HIF-1α/EMT related proteins HIF-1α, E-cd, Claudin-4, and VIM. The results indicated that YAF significantly enhanced expression of E-cd and Claudin-4,but decreased expression of HIF-1α, VIM in a dose-dependent manner. CONCLUSIONS: In conclusion, this study provided the first direct evidence that YAF inhibited the formation of VM in human CRC, suggesting that YAF may be considered as a useful target for cancer therapy.


Assuntos
Neoplasias Colorretais/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Células HCT116 , Humanos , Camundongos , Camundongos Nus , Neovascularização Patológica/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
17.
IUBMB Life ; 67(3): 191-201, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25873402

RESUMO

Chemoresistance of colon cancer cells to the chemotherapeutics is still a main obstacle in treatment of this malignancy. The microRNA (miRNA) mediated chemosensitivity regulation in colon cancer cells is still largely unknown. Here we constructed a fluorouracil (5-Fu) resistant SW480 cell line (SW480/5-Fu) and discovered that miRNA miR-494 was down-regulated in the drug resistant cells compared with the parental cells. miR-494 level was found to be correlated with 5-Fu sensitivity in colon cancer cells, and artificial alteration of miR-494 affects the sensitivity of colon cancer cell lines to 5-Fu. miR-494 also promoted apoptosis of colon cancer cells at present of 5-Fu. Importantly, as a regulatory enzyme in the 5-Fu catabolic pathway, DPYD was confirmed to be a direct target of miR-494 through the interaction of miR-494 and its binding site within DPYD 3' untranslated region (3'UTR). miR-494 also negatively regulated endogenous DPYD expression in SW480 cells. Overexpression or knockdown of DPYD could attenuate miR-494 mediated 5-Fu sensitivity regulation, suggesting the dependence of DPYD regulation in miR-494 activity. miR-494 inhibited SW480/5-Fu derived xenograft tumors growth in vivo at present of 5-Fu. Thus, we concluded that in colon cancer cells, tumor suppressor miR-494 enhanced 5-Fu sensitivity via regulation of DPYD expression.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Di-Hidrouracila Desidrogenase (NADP)/genética , Resistencia a Medicamentos Antineoplásicos/genética , Fluoruracila/farmacologia , MicroRNAs/genética , Regiões 3' não Traduzidas , Animais , Antimetabólitos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral/efeitos dos fármacos , Neoplasias do Colo/patologia , Di-Hidrouracila Desidrogenase (NADP)/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos Nus , MicroRNAs/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Tumour Biol ; 36(2): 1313-21, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25355599

RESUMO

Colorectal cancer (CRC, also known as colon cancer, rectal cancer, or bowel cancer) is the second leading cause of cancer mortality in the Western world. MicroRNAs (miRNAs) are a class of small (18-25 nucleotides long) noncoding RNAs with important posttranscriptional regulatory functions. miRNAs play important roles in various physiological and pathological processes including carcinogenesis in various solid cancers including CRC. In order to investigate the roles that miRNAs played in CRC, the expression of human miRNAs (in 20 normal adjacent tissue samples and 20 colon cancer samples) was examined in this study. miR-455, miR-484, and miR-101 were significantly downregulated in colon cancer samples. And overexpression of miR-455 significantly inhibited the proliferation and the invasion of SW480, but had no effect on apoptosis. PCR and Western blot showed that overexpression of miR-455 decreased protein expression of RAF proto-oncogene serine/threonine-protein kinase (RAF1) but had no effect on mRNA level. Luciferase assay indicated that miR-455 regulated RAF1 expression directly. Moreover, overexpression of RAF1 partially reversed the inhibitory effect of miR-455 on the growth and the invasion of SW480. The data indicated that miR-455 regulates the proliferation and invasion of colorectal cancer cells, at least in part, by downregulating RAF1, a direct target of miR-455. Collectively, our study demonstrated that miR-455-RAF1 may represent a new potential therapeutic target for colorectal carcinoma treatment.


Assuntos
Proliferação de Células , Neoplasias Colorretais/genética , MicroRNAs/biossíntese , Proteínas Proto-Oncogênicas c-raf/biossíntese , Apoptose/genética , Linhagem Celular Tumoral , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Invasividade Neoplásica/genética , Proto-Oncogene Mas
19.
Tumour Biol ; 35(12): 12467-72, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25185654

RESUMO

The purpose of the present study was to detect the expression levels of circulating miR-148a in the peripheral blood of osteosarcoma patients and to further investigate the clinicopathological, diagnostic, and prognostic value of miR-148a. Eighty-nine patients with initially diagnosed osteosarcoma who successfully underwent surgical resection were enrolled in this prospective study. The expression levels of circulating miR-148a were detected by real-time quantitative RT-PCR. All statistical analyses were performed with SPSS 18.0 statistical software to determine the potential values of circulating miR-148a on the clinicopathological factors, diagnosis, and prognosis. The expression levels of circulating miR-148a in osteosarcoma patients were significantly higher than that in the healthy controls (P < 0.001), and miR-148a was capable of distinguishing osteosarcoma patients from healthy controls effectively (AUC = 0.783). In addition, miR-148a expression was significantly associated with tumor size (P = 0.049) and distant metastasis (P = 0.004). Univariate survival analysis demonstrated that patients with miR-148a high expression had significantly poor overall survival (P < 0.001) and disease-specific survival (P < 0.001) after 5 years' operation. Multivariate survival analysis confirmed that miR-148a high expression was an independent predictor for unfavorable overall survival (P = 0.003) and disease-specific survival (P = 0.008), respectively. Our findings demonstrated that detection of circulating miR-148a expression in the peripheral blood have clinical potentials as an indicator of progressive phenotype, a novel diagnostic biomarker and a promising predictor to identify individuals with poor prognosis for osteosarcoma patients.


Assuntos
Biomarcadores Tumorais , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/genética , MicroRNAs/genética , Osteossarcoma/diagnóstico , Osteossarcoma/genética , Adolescente , Adulto , Neoplasias Ósseas/sangue , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Feminino , Seguimentos , Humanos , Masculino , MicroRNAs/sangue , Metástase Neoplásica , Osteossarcoma/sangue , Osteossarcoma/tratamento farmacológico , Osteossarcoma/mortalidade , Prognóstico , Curva ROC , Carga Tumoral , Adulto Jovem
20.
Exp Gerontol ; 193: 112467, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38797287

RESUMO

OBJECTIVE: To investigate the cognitive function and nutritional status of elderly patients with gastric cancer during perioperative period, and to analyze their correlation. METHODS: Aged patients undergoing gastric cancer surgery in The Affiliated Cancer Hospital of Shandong First Medical University from March to October 2021 were selected as the subjects of this study. The monitoring data of cognitive function and nutritional status were retrospectively analyzed from 1 to 3 days before surgery, 1 and 3 days after surgery, 7 days after surgery (before discharge) and 30 days after surgery to analyze the correlation between cognitive function and nutritional status in elderly patients with gastric cancer. RESULTS: the incidence of mild cognitive impairment in elderly patients with gastric cancer was 52.43 %, the visual space of the two groups' (mild cognitive impairment) ability of execution, name, attention, language, abstract thinking, delayed memory and cognitive function scores were lower than 1 set of directional force (cognitive function in normal group), statistically significant difference (P < 0.05). The nutritional status of elderly patients with gastric cancer was lower than that of healthy elderly group at the same period (P < 0.05). The scores of visual spatial executive function, name, attention, delayed memory, orientation and total score of cognitive function in elderly gastric cancer patients were positively correlated with nutritional status (P < 0.05). CONCLUSIONS: The cognitive function and nutritional status of elderly patients with gastric cancer are both in a low state during treatment and a higher level of cognitive function can help patients maintain a more correct nutritional cognition, and the nutritional status of patients will be relatively better. There is a positive correlation between cognitive function and nutritional status in elderly patients with gastric cancer, which should be paid attention to in the treatment.


Assuntos
Cognição , Disfunção Cognitiva , Estado Nutricional , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/psicologia , Feminino , Masculino , Idoso , Estudos Retrospectivos , Disfunção Cognitiva/etiologia , Período Perioperatório , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade
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