MARVELD1 inhibited cell proliferation and enhance chemosensitivity via increasing expression of p53 and p16 in hepatocellular carcinoma.
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.
School of Life Science and Biotechnology, Harbin Institute of Technology, Harbin, Heilongjiang, China.
Youtao
Y
Yu
Yubao
Y
Zhang
Jianran
J
Hu
Hao
H
Zhang
Shan
S
Wang
Fang
F
Han
Lei
L
Yue
Youpeng
Y
Qu
Yao
Y
Zhang
Hongjian
H
Liang
Huan
H
Nie
Yu
Y
Li
D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D018628:Gene Dosage; D019942:Genes, p16; D016158:Genes, p53; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008565:Membrane Proteins / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015854:Up-Regulation
C542435:MARVELD1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering