title: miR-16 promotes the apoptosis of human cancer cells by targeting FEAT.
abstract: BACKGROUND
  Although human cancers have heterogeneous combinations of altered oncogenes, some crucial genes are universally dysregulated in most cancers. One such gene, FEAT (faint expression in normal tissues, aberrant overexpression in tumors), is uniformly overexpressed in a variety of human cancers and plays an important role in tumorigenesis by suppressing apoptosis. However, the precise molecular mechanism through which FEAT is upregulated during tumorigenesis remains largely unknown.
  
  
  METHODS
  In this study, we used bioinformatic analyses to search for miRNAs that potentially target FEAT. We examined the expression of FEAT protein level by western blotting and miR-16 level by qRT-PCR assay. Cancer cell lines (A549, MCF-7 and Huh-7) with miR-16 upregulation and FEAT silencing were established and the effects on apoptosis of cancer cells in vitro were assessed. Luciferase reporter assay was also performed to investigate the interaction between miR-16 and FEAT.
  
  
  RESULTS
  We identified a specific target site for miR-16 in the 3'-untranslated region (3'-UTR) of FEAT. Consistent with the bioinformatic analyses, we identified an inverse correlation between the miR-16 and FEAT protein levels in lung cancer, breast cancer, and hepatocellular cancer tissues. We then experimentally validated miR-16 as a direct regulator of FEAT using cell transfection and luciferase assays. Finally, we demonstrated that the repression of FEAT by miR-16 promoted the apoptosis of cancer cells.
  
  
  CONCLUSIONS
  Our findings provide the first clues regarding the role of miR-16 as a tumor suppressor in cancer cells through the inhibition of FEAT translation.
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Liang
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093, China.|Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of General Surgery of Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu, 210008, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093, China.
authors.forename: Xueliang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093, China.
authors.forename: Suyang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093, China.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Comprehensive Cancer Center of Drum Tower Hospital Affiliated to Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, 210008, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of General Surgery of Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu, 210008, China.
authors.forename: Wen-xian
authors.initials: WX
authors.lastname: Guan
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093, China.
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zen
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093, China. yjzhang@nju.edu.cn.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093, China. xichen@nju.edu.cn.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu, 210002, China. oxis@163.com.
authors.forename: Guangxin
authors.initials: G
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; C583021:EEF1AKNMT protein, human; D008780:Methyltransferases