MicroRNA-520b inhibits growth of hepatoma cells by targeting MEKK2 and cyclin D1.
Growing evidence indicates that the deregulation of microRNAs (miRNAs) contributes to the tumorigenesis. We previously revealed that microRNA-520b (miR-520b) was involved in the complement attack and migration of breast cancer cells. In this report, we show that miR-520b is an important miRNA in the development of hepatocellular carcinoma (HCC). Our data showed that the expression levels of miR-520b were significantly reduced in clinical HCC tissues and hepatoma cell lines. We observed that the introduction of miR-520b dramatically suppressed the growth of hepatoma cells by colony formation assays, 5-ethynyl-2-deoxyuridine (EdU) incorporation assays and 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Moreover, ectopic expression of miR-520b was able to inhibit the growth of hepatoma cells in nude mice. Further studies revealed that the mitogen-activated protein kinase kinase kinase 2 (MEKK2) and cyclin D1 were two of direct target genes of miR-520b. Silencing of MEKK2 or cyclin D1 was able to inhibit the growth of hepatoma cells in vitro and in vivo, which is consistent with the effect of miR-520b overexpression on the growth of hepatoma cells. In addition, miR-520b significantly decreased the phosphorylation levels of c-Jun N-terminal kinase (p-JNK, a downstream effector of MEKK2) or retinoblastoma (p-Rb, a downstream effector of cyclin D1). In conclusion, miR-520b is able to inhibit the growth of hepatoma cells by targeting MEKK2 or cyclin D1 in vitro and in vivo. Our findings provide new insights into the role of miR-520b in the development of HCC, and implicate the potential application of miR-520b in cancer therapy.
Department of Cancer Research, Key Laboratory of Molecular Microbiology and Technology of Ministry of Education, Institute for Molecular Biology, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
Weiying
W
Zhang
Guangyao
G
Kong
Junping
J
Zhang
Tao
T
Wang
Lihong
L
Ye
Xiaodong
X
Zhang
D000818:Animals; D000970:Antineoplastic Agents; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D048730:MAP Kinase Kinase Kinase 2; D020930:MAP Kinase Kinase Kinases / Q000187:drug effects*; D051379:Mice; D035683:MicroRNAs / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; C575048:MIRN520 microRNA, human; D035683:MicroRNAs; D019938:Cyclin D1; D048730:MAP Kinase Kinase Kinase 2; D020930:MAP Kinase Kinase Kinases; C482618:MAP3K2 protein, human