miR-449a inhibits colorectal cancer progression by targeting SATB2
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Xiaohua Sun1,*, Sanhong Liu1,8,*, Pengfei Chen1, Da Fu3, Yingyong Hou4, Jin Hu5, Zhi Liu1, Yuhang Jiang1, Xinwei Cao1, Chunyan Cheng1, Xi Chen1, Yu Tao1, Cuifeng Li1, Yiming Hu1, Zhanjie Liu1, Yu Zhan1, Jie Mao1, Qi Wang1, Yushui Ma6, Xianling Cong7, Ran Sun7, Yufang Shi1, Mingliang Wang5 and Xiaoren Zhang1,2
1Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, 200031, China
2Collaborative Innovation Center of System Biomedicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200240, China
3Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, 200031, China
4Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
5General Surgery Department, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
6Department of Nuclear Medicine, Shanghai 10th People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, China
7Tissue Bank, Scientific Research Center, China-Japan Union Hospital, Changchun, 130033, China
8Present address: Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210, China
*These authors contributed equally to this work
Xiaoren Zhang, email: firstname.lastname@example.org
Mingliang Wang, email: email@example.com
Keywords: colorectal cancer, miR-449a, SATB2, tumorigenesis
Received: January 15, 2016 Accepted: July 06, 2016 Published: July 28, 2016
miR-449a has been reported to act as a tumor suppressor in several cancers, however, it is controversial whether it inhibits tumor growth in colorectal cancer. The mechanisms underlying its expression and functions in colorectal cancers are still largely unknown. SATB2 is a sensitive and specific marker for CRC diagnosis. However, the mechanisms by which the expression and functions of SATB2 are regulated still remain to be clarified. We investigated the expression and functional significance of miR-449a and SATB2 and the mechanisms of their dysregulation in human CRC cells. miR-449a overexpression or SATB2 depletion inhibited tumor growth and promoted apoptosis in colorectal tumor cells in vitro and in xenograft mouse model, partially by downregulating SATB2. Expression of miR-449a was increased epigenetically via knocking down their targets, particularly SATB2. miR-449a was downregulated and STAB2 expression was upregulated in human CRCs. Their expressions were significantly associated with overall survival of CRC patients. Our findings demonstrate the existence of a miR-449a-SATB2 negative feedback loop that maintains low levels of miR-449a as well as high level of SATB2, thereby promoting CRC development.
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