title: miR-10b exerts oncogenic activity in human hepatocellular carcinoma cells by targeting expression of CUB and sushi multiple domains 1 (CSMD1).
abstract: Hepatocellular 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.
  
  
  
  Forty-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.
  
  
  
  miR-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.
  
  
  
  We 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.
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Li
authors.initials: L
authors.lastname: Gong
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Tu
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yao
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Jia-Rui
authors.initials: JR
authors.lastname: Zhang
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Han
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Shao-Jun
authors.initials: SJ
authors.lastname: Zhu
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Wang
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China. lyhzhw@fmmu.edu.cn.|Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China. lyhzhw@fmmu.edu.cn.|Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China. lyhzhw@fmmu.edu.cn.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Li
authors.affiliation: The Helmholtz Sino-German Laboratory for Cancer Research, Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China. zhwlyh@fmmu.edu.cn.|Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China. zhwlyh@fmmu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009857:Oncogenes / Q000235:genetics; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins
chemical_list: D020413:3' Untranslated Regions; C477880:CSMD1 protein, human; C547183:MIRN10 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins
keywords: CSMD1; Hepatocellular carcinoma; Oncogene; miR-10b