title: MicroRNA-15a-5p suppresses cancer proliferation and division in human hepatocellular carcinoma by targeting BDNF.
abstract: We examined the expression pattern and functional roles of microRNA 15a-5p (miR-15a-5p) in human hepatocellular carcinoma (HCC). Possible miR-15a-5p aberrant expression in HCC cell lines or clinical HCC specimens was examined by quantitative real-time PCR (qRT-PCR). In HCC HepG2 and SNU-182 cells, miR-15a-5p was ectopically overexpressed by lentiviral transduction. Its effect on HCC proliferation, cancer division, and in vivo tumor growth were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle assay, and tumorigenicity assay, respectively. The targeting of miR-15a-5p on its downstream gene, brain-derived neurotrophic factor (BDNF), was examined by dual-luciferase assay, qRT-PCR, and Western blot, respectively. BDNF was then overexpressed in HepG2 and SNU-182 cells to evaluate its selective effect on miR-15a-5p in HCC modulation. MiR-15a-5p is aberrantly downregulated in in vitro HCC cell lines and in vivo HCC clinical specimens. Ectopic overexpression of miR-15a-5p suppressed cancer proliferation, induced cell cycle arrest in HepG2 or SNU-182 cells in vitro, and inhibited HCC tumor growth in vivo. MiR-15a-5p selectively and negatively regulated BDNF at both gene and protein levels in HCC cells. Forced overexpression of BDNF effectively reversed the tumor suppressive functions of miR-15a-5p on HCC proliferation and cell division in vitro. Our study demonstrated that miR-15a-5p is a tumor suppressor in HCC and its regulation is through BDNF in HCC.
authors.affiliation: Department of Medicinal Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
authors.forename: Jianting
authors.initials: J
authors.lastname: Long
authors.affiliation: Department of Hepatobiliary Surgery, Division of Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
authors.forename: Baoxian
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, Division of Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. fangshi@mail.sysu.edu.cn.|Department of Clinic Nutrition, The First Affiliated Hospital of Sun Yat-sen University, 58 2nd Zhongshan Rd, Guangzhou, 510080, China. fangshi@mail.sysu.edu.cn.
authors.forename: Shi
authors.initials: S
authors.lastname: Fang
authors.affiliation: Department of Hepatobiliary Surgery, Division of Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. kuangm@mail.sysu.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Kuang
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D002455:Cell Division; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005822:Genetic Vectors; D056945:Hep G2 Cells / Q000637:transplantation; D006801:Humans; D016086:Lentivirus; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D012334:RNA, Neoplasm / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C505361:MIRN15 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; C579455:BDNF protein, human
keywords: BDNF; Cancer proliferation; Cell cycle; Hepatocellular carcinoma; miR-15a-5p