title: miR-486 regulates metastasis and chemosensitivity in hepatocellular carcinoma by targeting CLDN10 and CITRON.
abstract: OBJECTIVE
  miRNA-486 (miR-486) was first identified from the human fetal liver cDNA library and considered to be associated with hepatocellular carcinoma (HCC) development. Its roles in regulation of HCC metastasis and chemosensitivity have not been explored yet.
  
  
  METHODS
  miR-486 expression in HCC tissues, cell lines and serum was evaluated by real-time polymerase chain reaction. miR-486 overexpression or downregulation in the cell lines SMMC-7721/LM3 was conducted by lentivirus transfection. Cell proliferation, migration and apoptosis were quantitated using commercial assays. Matrix metalloproteinase activity was quantitated by gelatin zymography. The target genes of miR-486 were screened by 3'-untranslated region luciferase report assays and their function was validated by small RNA interference.
  
  
  RESULTS
  We show here that miR-486 is frequently down-expressed in HCC tissues and cell lines. Lentivirus-mediated restoration of miR-486 in HCC cell lines resulted in significant reduction in the ability of cell growth, colony formation and migration. However, miR-486 inhibition enhances proliferation and invasion of HCC cells. Two genes, CITRON and CLDN10 which regulate cell proliferation and invasion, respectively, were identified as the direct targets of miR-486 in HCC cells. CITRON and CLDN10 knockdown by siRNA results in similar phenotypes of miR-486 restoration in HCC cell lines. In addition, miR-486 enhances the chemosensitivity of HCC cells to sorafenib.
  
  
  CONCLUSIONS
  Our data indicated that miR-486 may function as a novel tumor suppressor in HCC.
authors: Departments of Experimental Hematology, Beijing, China.
authors: Huiyan
authors: H
authors: Sun
authors: Departments of Experimental Hematology, Beijing, China.
authors: Chunping
authors: C
authors: Cui
authors: Departments of Experimental Hematology, Beijing, China.
authors: Fengjun
authors: F
authors: Xiao
authors: Departments of Experimental Hematology, Beijing, China.
authors: Hua
authors: H
authors: Wang
authors: Departments of Experimental Hematology, Beijing, China.
authors: Jun
authors: J
authors: Xu
authors: Departments of Experimental Hematology, Beijing, China.
authors: Xuefeng
authors: X
authors: Shi
authors: Departments of Experimental Hematology, Beijing, China.
authors: Yuefeng
authors: Y
authors: Yang
authors: Departments of Experimental Hematology, Beijing, China.
authors: Qunwei
authors: Q
authors: Zhang
authors: Biochemistry and Molecular Biology, Beijing Institute of Radiation Medicine, Beijing, China.
authors: Xiaofei
authors: X
authors: Zheng
authors: Biochemistry and Molecular Biology, Beijing Institute of Radiation Medicine, Beijing, China.
authors: Xiaoming
authors: X
authors: Yang
authors: Departments of Experimental Hematology, Beijing, China.|Department of Respiratory Diseases, Qinghai Provincial People's Hospital, Xining, China.
authors: Chutse
authors: C
authors: Wu
authors: Departments of Experimental Hematology, Beijing, China.|Department of Respiratory Diseases, Qinghai Provincial People's Hospital, Xining, China.
authors: Lisheng
authors: L
authors: Wang
keywords: CITRON; CLDN10; hepatocellular carcinoma; miRNA-486; migration; sorafenib