IGF2-derived miR-483 mediated oncofunction by suppressing DLC-1 and associated with colorectal cancer
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Hengmi Cui1,2,7,*, Yuan Liu2,3,5,*, Jingrui Jiang2,3,6,*, Yangyang Liu1,2, Zhe Yang1,2, Shaogen Wu2,3, Wangsen Cao2, Isabelle H. Cui4, Chenggong Yu2,3
1Institute of Epigenetics and Epigenomics, Institute of Comparative Medicine and College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China
2Laboratory of Epigenetics & Epigenomics, Medical School, Nanjing University, Nanjing, China
3Department of Gastroenterology, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing, China
4Department of Pathology and Laboratory Medicine, New York Presbyterian-Weill Cornell Medicine, New York, USA
5Quzhou People’s Hospital, Quzhou, Zhengjiang, China
6Xuzhou Cancer Hospital, Xuzhou, Jiangsu, China
7Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
*These authors have contributed equally to this work
Hengmi Cui, email: [email protected]
Chenggong Yu, email: [email protected]
Keywords: IGF2, miR-483, colorectal cancer, DLC-1
Received: February 15, 2016 Accepted: June 09, 2016 Published: June 27, 2016
Emerging evidence indicates that IGF2 plays an important role in various human malignancies, including colorectal cancer (CRC). Hsa-miR-483 is located within intron 7 of the IGF2 locus. However, the mechanism by which increased IGF2 induces carcinogenesis remains largely elusive. DLC-1 has been identified as a candidate tumor suppressor. In this study, we aimed at investigating whether miR-483 transcription is IGF2-dependent, identifying the functional target of miR-483, and evaluating whether tissue and serum miR-483-3p or miR-483-5p levels are associated with CRC. Our results showed that sequences upstream miR-483 had undetectable promoter activity and levels of IGF2, miR-483-3p, and miR-483-5p were synchronously increased in CRC tissues. Positive correlations between IGF2 and miR-483-3p (r=0.4984, ***p<0.0001), and between IGF2 and miR-483-5p (r=0.6659, ***p<0.0001) expression were found. In addition, patients with CRC had a significantly higher serum miR-483-5p level (*p<0.05) compared to normal controls. DLC-1 expression was decreased in colorectal cancer tissues and diminished through transient transfection with miR-483-3p. Our results suggest that IGF2 may exert its oncofunction, at least partly, through its parasitic miR-483 which suppressed DLC-1 in CRC cells. Thus, miR-483 might serve as a new target for therapy and a potential biomarker for the detection of colorectal cancer.
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