title: MicroRNA-21 promotes cell proliferation in human hepatocellular carcinoma partly by targeting HEPN1.
abstract: It has been reported that miR-21 is upregulated in hepatocellular carcinoma (HCC), and overexpressed miR-21 plays a key role in promoting cell cycle progression, reducing cell death and favoring angiogenesis and invasion. Overexpression of hepatocellular carcinoma, downregulated 1 (HEPN1) exhibits an antiproliferative effect on HepG2 cells, suggesting that silencing of HEPN1 may contribute to carcinogenesis of hepatocytes. In silico analysis revealed that HEPN1 may be a potential target of miR-21. Using quantitative reverse transcription PCR and Western blot, we found that HEPN1 was strikingly downregulated in both mRNA (fold change was 33.5, P < 0.0001) and protein levels in human HCC tumor tissues, in comparison with the adjacent non-tumor tissues. More importantly, the expression level of HEPN1 was inversely correlated with the expression of miR-21 in HCC (R (2) = 0.442, P < 0.0001). The combination between the 3' untranslated region (UTR) of HEPN1 with miR-21 was experimentally verified by a miRNA luciferase reporter approach. The suppressed cell proliferation upon stimulation of miR-21 inhibitor could be partially abolished by knocking down HEPN1, so inhibition of miR-21 expression in HCC cells profoundly suppressed cell proliferation partially by upregulating HEPN1 expression. Taken together, the current study suggested an underlying mechanism that miR-21 directly target HEPN1 and inhibit its expression during the carcinogenesis of HCC. HEPN1 may thus be a candidate as a therapeutic target for patients with HCC.
authors: Department of Forensic Medicine, Medical College of Soochow University, Suzhou, 215123, Jiangsu, People's Republic of China.
authors: Shuxiang
authors: S
authors: Hu
authors: Ruiyang
authors: R
authors: Tao
authors: Shouyu
authors: S
authors: Wang
authors: Chaoqun
authors: C
authors: Wang
authors: Xiankun
authors: X
authors: Zhao
authors: Hua
authors: H
authors: Zhao
authors: Lijuan
authors: L
authors: Li
authors: Shaohua
authors: S
authors: Zhu
authors: Yan
authors: Y
authors: He
authors: Xinghong
authors: X
authors: Jiang
authors: Yuzhen
authors: Y
authors: Gao
mesh_terms: D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: C549604:HEPN1 protein, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D011506:Proteins; D012333:RNA, Messenger