PMID- 26581909 OWN - NLM STAT- MEDLINE DCOM- 20170203 LR - 20181113 IS - 1423-0380 (Electronic) IS - 1010-4283 (Linking) VI - 37 IP - 5 DP - 2016 May TI - MicroRNA-15a-5p suppresses cancer proliferation and division in human hepatocellular carcinoma by targeting BDNF. PG - 5821-8 LID - 10.1007/s13277-015-4427-6 [doi] AB - 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. FAU - Long, Jianting AU - Long J AD - Department of Medicinal Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. FAU - Jiang, Chunlin AU - Jiang C AD - Department of Hepatobiliary Surgery, Division of Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. FAU - Liu, Baoxian AU - Liu B AD - Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. FAU - Fang, Shi AU - Fang S AD - Department of Hepatobiliary Surgery, Division of Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. fangshi@mail.sysu.edu.cn. AD - 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. FAU - Kuang, Ming AU - Kuang M AD - Department of Hepatobiliary Surgery, Division of Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. kuangm@mail.sysu.edu.cn. LA - eng PT - Journal Article DEP - 20151118 PL - Netherlands TA - Tumour Biol JT - Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine JID - 8409922 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (MIRN15 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Neoplasm Proteins) RN - 0 (RNA, Neoplasm) RN - 0 (Recombinant Fusion Proteins) RN - 7171WSG8A2 (BDNF protein, human) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*physiology MH - Carcinoma, Hepatocellular/genetics/*pathology MH - Cell Division MH - Cell Line, Tumor MH - Down-Regulation MH - Female MH - Gene Expression Regulation, Neoplastic MH - Genes, Tumor Suppressor MH - Genetic Vectors MH - Hep G2 Cells/transplantation MH - Humans MH - Lentivirus MH - Liver Neoplasms/genetics/*pathology MH - Mice MH - Mice, Nude MH - MicroRNAs/*genetics MH - Neoplasm Proteins/genetics/*physiology MH - RNA, Neoplasm/*genetics MH - Recombinant Fusion Proteins/metabolism OTO - NOTNLM OT - BDNF OT - Cancer proliferation OT - Cell cycle OT - Hepatocellular carcinoma OT - miR-15a-5p EDAT- 2015/11/20 06:00 MHDA- 2017/02/06 06:00 CRDT- 2015/11/20 06:00 PHST- 2015/09/24 00:00 [received] PHST- 2015/11/10 00:00 [accepted] PHST- 2015/11/20 06:00 [entrez] PHST- 2015/11/20 06:00 [pubmed] PHST- 2017/02/06 06:00 [medline] AID - 10.1007/s13277-015-4427-6 [pii] AID - 10.1007/s13277-015-4427-6 [doi] PST - ppublish SO - Tumour Biol. 2016 May;37(5):5821-8. doi: 10.1007/s13277-015-4427-6. Epub 2015 Nov 18.