title: Deregulation of the miR-16-KRAS axis promotes colorectal cancer.
abstract: KRAS plays a significant role in the etiology and progression of colorectal cancer (CRC), but the mechanism underlying this process has not been fully elucidated. In this study, we found that the KRAS protein levels were higher in CRC tissues than in the normal adjacent tissues, whereas its mRNA levels varied irregularly, suggesting that a post-transcriptional mechanism is involved in the regulation of KRAS. Then, we performed bioinformatic analyses to search for miRNAs that potentially target KRAS. We predicted and experimentally validated that miR-16 directly recognizes the 3'-UTR of the KRAS transcript and regulates KRAS expression. Furthermore, the in vitro results showed that the repression of KRAS by miR-16 suppressed the proliferation and invasion and induced the apoptosis of CRC cells, and the in vivo results revealed that miR-16 exerted a tumor-suppressive effect by negatively regulating KRAS in xenograft mice. Taken together, our findings provide evidence supporting the role of miR-16 as a tumor suppressor in CRC by targeting KRAS.
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Tiyuanbei, Tianjin, 300060, China.|State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210046, China.
authors.forename: Chaoying
authors.initials: C
authors.lastname: You
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210046, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Liang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Tiyuanbei, Tianjin, 300060, China.|State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210046, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Gastroenterology, Tianjin First Center Hospital, 24 Fukang Road, Tianjin, 300192, China.
authors.forename: Jialu
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210046, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Tiyuanbei, Tianjin, 300060, China.|State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210046, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Tiyuanbei, Tianjin, 300060, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Tiyuanbei, Tianjin, 300060, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yue
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210046, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210046, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Huanhuxi Road, Tiyuanbei, Tianjin, 300060, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ba
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D016283:Proto-Oncogene Proteins p21(ras)