title: miR-383 inhibits hepatocellular carcinoma cell proliferation via targeting APRIL.
abstract: Mounting evidence has shown that microRNAs (miRNAs), a class of small non-coding RNAs, are frequently deregulated in human malignancies and have pivotal roles in diverse biological processes including cancer cell proliferation. Herein, we investigated the expression pattern of miR-383 in 64 hepatocellular carcinoma (HCC) tissues and 4 HCC cell lines and found that miR-383 was downregulated in HCC tissues and cell lines. Moreover, miR-383 expression in HCC was significantly correlated with tumor size and tumor-node-metastasis (TNM) stage. Kaplan-Meier analysis showed that decreased miR-383 expression was associated with poor overall survival of HCC patients. In addition, Cox regression analysis indicated that miR-383 was an independent prognostic factor for HCC patients. Then, functional studies demonstrated that ectopic miR-383 expression could significantly suppress the in vitro proliferation of HCC cells, as well as induce cell cycle arrest and cell apoptosis. Luciferase reporter assay further identified that a proliferation-inducing ligand (APRIL), a member in the tumor necrosis factor (TNF) superfamily, was a novel target gene for miR-383. Subsequent investigation revealed that miR-383 expression was inversely correlated with APRIL messenger RNA (mRNA) expression in HCC tissues. Besides, recombinant human APRIL (rhAPRIL) could rescue HCC cell proliferation inhibited by miR-383. Taken together, our present study provided the first evidence that miR-383 was decreased in HCC and associated with tumor progression and prognosis of HCC patients. Furthermore, our findings confirmed that miR-383 might inhibit HCC cell proliferation partially via downregulating APRIL expression. Thus, this study might provide a promising strategy by targeting with the miR-383-APRIL axis in the treatment of HCC.
authors.affiliation: Department of Gastroenterology and Clinical Laboratory, The Third People's Hospital of Nantong City, Jiangsu, 226006, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology and Clinical Laboratory, The Third People's Hospital of Nantong City, Jiangsu, 226006, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Gastroenterology and Clinical Laboratory, The Third People's Hospital of Nantong City, Jiangsu, 226006, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Gastroenterology and Clinical Laboratory, The Third People's Hospital of Nantong City, Jiangsu, 226006, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Gastroenterology and Clinical Laboratory, The Third People's Hospital of Nantong City, Jiangsu, 226006, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Shao
authors.affiliation: Department of Clinical Laboratory Center, Affiliated Hospital of Nantong University, Jiangsu, 226001, China. richardwangf@163.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics*
chemical_list: C558685:MIRN383 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C114631:TNFSF13 protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13
keywords: APRIL; Apoptosis; Cell cycle; Cell proliferation; Hepatocellular carcinoma; miR-383