title: Igf2-derived intronic miR-483 promotes mouse hepatocellular carcinoma cell proliferation.
abstract: Most intronic micro-RNAs are coexpressed with their host genes, suggesting that they may play similar roles. The function of miR-483 remains unknown, although it is embedded in an intron of Igf2 gene, which is an activator of hepatocellular carcinoma proliferation. In the present study, we provide evidence that Igf2-derived miR-483 can induce proliferation in hepatocellular carcinoma cells. The miR-483 promotion of proliferation was analysed by soft agar colony formation assay and proliferation curve assay. The effect of miR-483 on Socs3 expression was examined by Western blot and a reporter assay. Our results revealed that Igf2-derived intronic miR-483 was identified by the application of 94G6, an inhibitor of Igf2 at the transcriptional level. All results from the (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) MTT assay, the proliferation curve assay and the soft agar colony formation assay showed that miR-483 promoted the proliferation of hepatocellular carcinoma cells. Finally, Socs3, a putative target predicted by bioinformatics, was regulated by miR-483 at mRNA and protein levels. Direct binding with the 3' UTR was identified by a luciferase activity assay. Our findings demonstrate that Igf2-derived intronic miR-483, through downregulation of its target Socs3, regulates hepatoma cell proliferation and thus may serve as a potential target for hepatocellular carcinoma therapy.
authors: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors: Ning
authors: N
authors: Ma
authors: Fuyuan
authors: F
authors: Li
authors: Dan
authors: D
authors: Li
authors: Yang
authors: Y
authors: Hui
authors: Xidi
authors: X
authors: Wang
authors: Yu
authors: Y
authors: Qiao
authors: Yanfen
authors: Y
authors: Zhang
authors: Ying
authors: Y
authors: Xiang
authors: Jianying
authors: J
authors: Zhou
authors: Lingyun
authors: L
authors: Zhou
authors: Xiaofei
authors: X
authors: Zheng
authors: Xu
authors: X
authors: Gao
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D007438:Introns; D008113:Liver Neoplasms; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C513121:IGF2 protein, mouse; D035683:MicroRNAs; C548913:Mirn483 microRNA, mouse; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D007335:Insulin-Like Growth Factor II