miR-10b exerts oncogenic activity in human hepatocellular carcinoma cells by targeting expression of CUB and sushi multiple domains 1 (CSMD1)

BMC Cancer

Research Article

Qian Tu¹  Xiu-Juan Han¹  Li Gong¹  Shao-Jun Zhu¹  Qiao Zhu¹  Jia-Rui Zhang¹  Shu-Mei Wang¹  Jun Wang¹  Li Yao¹  Yan-Hong Li²  Wei Zhang³ 

[1] The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, 710038, Xi’an, China;The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, 710038, Xi’an, China;Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 710038, Xi’an, China;Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, 710038, Xi’an, China;The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, 710038, Xi’an, China;Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, 710038, Xi’an, China;

关键词: Hepatocellular carcinoma;    miR-10b;    CSMD1;    Oncogene;   

DOI  :  10.1186/s12885-016-2801-4

 received in 2016-01-14, accepted in 2016-09-22,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundHepatocellular carcinoma (HCC) is a lethal disease, while the precise underlying molecular mechanisms of HCC pathogenesis remain to be defined. MicroRNA (miRNA), a class of non-coding small RNAs, can post-transcriptionally regulate gene expression. Altered miRNA expression has been reported in HCCs. This study assessed expression and the oncogenic activity of miRNA-10b (miR-10b) in HCC.MethodsForty-five paired human HCC and adjacent non-tumor tissues were collected for qRT-PCR and immunohistochemistry analysis of miR-10b and CUB and Sushi multiple domains 1 (CSMD1), respectively. We analyzed the clinicopathological data from these patients to further determine if there was an association between miR-10b and CSMD1. HCC cell lines were used to assess the effects of miR-10b mimics or inhibitors on cell viability, migration, invasion, cell cycle distribution, and colony formation. Luciferase assay was used to assess miR-10b binding to the 3’-untranslated region (3’-UTR) of CSMD1.ResultsmiR-10b was highly expressed in HCC tissues compared to normal tissues. In vitro, overexpression of miR-10b enhanced HCC cell viability, migration, and invasion; whereas, downregulation of miR-10b expression suppressed these properties in HCC cells. Injection of miR-10b mimics into tumor cell xenografts also promoted xenograft growth in nude mice. Bioinformatics and luciferase reporter assay demonstrated that CSMD1 was the target gene of miR-10b. Immunocytochemical, immunohistochemical, and qRT-PCR data indicated that miR-10b decreased CSMD1 expression in HCC cells.ConclusionsWe showed that miR-10b is overexpressed in HCC tissues and miR-10b mimics promoted HCC cell viability and invasion via targeting CSMD1 expression. Our findings suggest that miR-10b acts as an oncogene by targeting the tumor suppressor gene, CSMD1, in HCC.

【 授权许可】

CC BY   
© The Author(s). 2016