机构：[1]Department of Molecular Biology, Shanxi Cancer Hospital and Institute, Shanxi, China[2]School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NewSouth Wales, Australia[3]School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia[4]Department of Pathophysiology, School ofPreclinical and Forensic Medicine, Sichuan University, Chengdu, China and 5School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales,Australia.
Despite advances in early diagnosis and the development of molecularly targeted therapy, curative treatment of colon cancer once it has metastasized is yet to be accomplished. This is closely associated with deregulated CRC cell proliferation and resistance to apoptosis. Here we reveal that upregulation of microRNA-645 (miR-645) through DNA copy number gain is responsible for enhanced proliferation and resistance to apoptosis in colon cancer. MiR-645 was upregulated in most colon cancer tissues related to adjacent normal mucosa. This appeared to be associated with amplification of a section of chromosome 20q13.13, where miR-645 is located. Inhibition of miR-645 reduced proliferation and enhanced sensitivity to apoptosis triggered by the chemotherapeutic drugs 5-fluorouracil and cisplatin in CRC cells, and retarded colon cancer xenograft growth. Conversely, overexpression of miR-645 in normal colon epithelial cells enhanced proliferation and triggered anchorage-independent cell growth. Although SRY-related HMG-box 30 (SOX30) was identified as a miR-645 target, its expression was only partially affected by miR-645, suggesting that miR-645 is a fine-tuning mechanism of SOX30 expression. Moreover, overexpression of SOX30 only moderately inhibited promotion of CRC cell proliferation by miR-645, indicating that miR-645 may have more targets that contribute to its pro-proliferation effect in colon cancer. Together, this study reveals that miR-645 can regulate oncogenesis in colon cancer with SOX30 being one of its targets.
基金：
the National Health and Medical Research Council
(NHMRC) (APP1026458), the Cancer Council NSW (RG13-04 and RG 13-15), Australia,
and the Shanxi Scholarship Council (2013-133) and Shanxi Natural Science
Foundation (201601D202101), China.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2017]版：
大类|2 区医学
小类|3 区肿瘤学
最新[2023]版：
大类|2 区医学
小类|2 区肿瘤学
第一作者：
第一作者机构：[1]Department of Molecular Biology, Shanxi Cancer Hospital and Institute, Shanxi, China[2]School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NewSouth Wales, Australia
通讯作者：
通讯机构：[1]Department of Molecular Biology, Shanxi Cancer Hospital and Institute, Shanxi, China[2]School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NewSouth Wales, Australia[*1]Department of Molecular Biology, Shanxi Cancer Hospital and Institute, Taiyuan, Shanxi 030013, China[*2]School of Biomedical Sciences and Pharmacy, University of Newcastle, LS3-49, Life Science Building, Callaghan, New South Wales 2308, Australia
推荐引用方式(GB/T 7714)：
ST Guo,XY Guo,J Wang,et al.MicroRNA-645 is an oncogenic regulator in colon cancer.[J].Oncogenesis.2017,6(5):e335.doi:10.1038/oncsis.2017.37.
APA：
ST Guo,XY Guo,J Wang,CY Wang,RH Yang...&CC Jiang.(2017).MicroRNA-645 is an oncogenic regulator in colon cancer..Oncogenesis,6,(5)
MLA：
ST Guo,et al."MicroRNA-645 is an oncogenic regulator in colon cancer.".Oncogenesis 6..5(2017):e335
