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MARVELD1 inhibited cell proliferation and enhance chemosensitivity via increasing expression of p53 and p16 in hepatocellular carcinoma.

ABSTRACT: We have previously found that expression of MARVELD1 was remarkably downregulated in multiple tumor tissues, but unclear in hepatocellular carcinoma (HCC) and its function has not been explored yet. In the present study, to uncover the underlying mechanism of MARVELD1 in the pathogenesis and development of HCC, we investigated the expression pattern of MARVELD1 and its effect on tumor proliferation in HCC. The results indicated the frequent downregulation of MARVELD1 in clinic samples and cell lines of HCC resulted from promoter methylation, as well as genetic deletion. Furthermore, treatment of MARVELD1 unexpressing Hep3B2.1-7 and PLC/PRF/5 cells with the demethylating agent 5-aza-2' deoxycytidine restored its expression. Overexpression of MARVELD1 suppressed the proliferation of HCC cells in vitro and in vivo, whereas downregulation of endogenous MARVELD1 by shRNAs significantly enhanced these characters. MARVELD1 overexpression could enhance chemosensitivity of HCC cells to epirubicin and 10-hydroxycamptothecin. Corresponding to these results, the expression of p-ERK1/2 and cyclin D1 were decreased, whereas p16 and p53 were increased in MARVELD1-transfected cells. We also demonstrated that knockdown of MARVELD1 resulted in upregulation of p-ERK1/2 and cyclin D1, and downregulation of p16 and p53. Moreover, the effect of the decreased cell growth rate was significantly reversed when MARVELD1-overexpressing cells were trasfected with p53 or p16 siRNA. Our findings suggest that MARVELD1 is a tumor suppressor by negatively regulating proliferation, tumor growth and chemosensitivity of HCC cells via increasing p53 and p16 in vitro and in vivo. MARVELD1 may be a potential target for HCC therapy.

SUBMITTER: Yu Y

PROVIDER: S-EPMC7659181 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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MARVELD1 inhibited cell proliferation and enhance chemosensitivity via increasing expression of p53 and p16 in hepatocellular carcinoma.

Yu Youtao Y Zhang Yubao Y Hu Jianran J Zhang Hao H Wang Shan S Han Fang F Yue Lei L Qu Youpeng Y Zhang Yao Y Liang Hongjian H Nie Huan H Li Yu Y

Cancer science 20120308 4

We have previously found that expression of MARVELD1 was remarkably downregulated in multiple tumor tissues, but unclear in hepatocellular carcinoma (HCC) and its function has not been explored yet. In the present study, to uncover the underlying mechanism of MARVELD1 in the pathogenesis and development of HCC, we investigated the expression pattern of MARVELD1 and its effect on tumor proliferation in HCC. The results indicated the frequent downregulation of MARVELD1 in clinic samples and cell l ...[more]

PMID: 22320884

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Project description:BackgroundCellular senescence-inhibited gene (CSIG) strongly prolongs the progression of replicative senescence. However, roles and mechanisms of CSIG in tumor progression have not been studied widely.MethodsRoles of CSIG in migration and proliferation of SMMC7721 and Huh7 cells were analyzed by transwell or cell viability assays, respectively. Tumorigenicity assays were used to study whether CSIG knockdown could affect SMMC7721 proliferation in vivo. Next, Western blotting and RT-PCR were preformed to evaluate the effects of CSIG on P-ERK cascade and epithelial mesenchymal transformation markers. Then, the location and expression of CSIG protein was detected by immunofluorescence and Western blotting, respectively. Finally, the Cancer Genome Atlas dataset was used to analyze CSIG mRNA levels in hepatocellular carcinoma (HCC) and adjacent non-tumor tissues.ResultsIn this study, we found that CSIG overexpression promoted SMMC7721 cell migration, and CSIG knockdown suppressed tumorigenicity of SMMC7721 cells. In contrast to expectation, CSIG up-regulation could significantly inhibit Huh7 cell growth and migration. CSIG could promote P-ERK activation and levels of mesenchymal-like markers in SMMC7721 cells, whereas CSIG suppressed P-ERK activation and levels of mesenchymal-like markers in Huh7 cells. CSIG protein was located in nucleoli as well as nucleoplasm of SMMC7721 cells, whereas CSIG protein was mainly expressed in the nucleoli rather than nucleoplasm of Huh7 cells. Finally, due to individual differences, raised or down-regulated trends of CSIG in HCC as compared with adjacent non-tumor tissues are different among various patient populations.ConclusionIn summary, these results indicate that CSIG might play different roles in SMMC7721 and Huh7 cells through regulating P-ERK pathway and mesenchymal-like markers. The differential distribution of CSIG might be an important factor that causes its different functions in SMMC7721 and Huh7 cells. CSIG might play different roles in various patient populations.

Dataset Information

MARVELD1 inhibited cell proliferation and enhance chemosensitivity via increasing expression of p53 and p16 in hepatocellular carcinoma.

Publications

MARVELD1 inhibited cell proliferation and enhance chemosensitivity via increasing expression of p53 and p16 in hepatocellular carcinoma.

Similar Datasets

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