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miR-491-5p functions as a tumor suppressor by targeting IGF2 in colorectal cancer

Authors Lu L, Cai M, Peng M, Wang F, Zhai X

Received 8 August 2018

Accepted for publication 4 December 2018

Published 22 February 2019 Volume 2019:11 Pages 1805—1816

DOI https://doi.org/10.2147/CMAR.S183085

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 2

Editor who approved publication: Dr Xueqiong Zhu


Lei Lu,* Ming Cai,* Meixia Peng, Fei Wang, Xiaofeng Zhai

Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, China

*These authors contributed equally to this work

Background: Dysregulation of miRNAs is critically implicated in tumorigenesis, and aberrant expression of miR-491-5p has been reported to play a key role in initiation and progression of various cancers. However, the biological function and underlying mechanism of miR-491-5p in colorectal cancer (CRC) remain elusive.
Methods: Quantitative real-time PCR (qRT-PCR) was employed to evaluate the levels of miR-491-5p and IGF2 mRNA expression in CRC tissues, cell lines and plasma. Cell counting kit-8 and colony formation assays were used to detect the effects of miR-491-5p on CRC cell growth. Luciferase reporter assays were applied to confirm the miR-491-5p target gene. In vivo experiments were conducted in nude mice.
Results: miR-491-5p was found to be obviously downregulated in CRC tissues and cell lines, and decreased miR-491-5p expression level was shown to be associated with differentiation, TNM stage and poor overall survival (OS). miR-491-5p overexpression suppressed CRC cell proliferation both in vitro and in vivo. Mechanically, insulin-like growth factor 2 (IGF2) was identified to be a direct target of miR-491-5p in CRC cells, and overexpression of IGF2 rescued the miR-491-5p-induced suppression of proliferation in CRC cells. Finally, we demonstrated that plasma miR-491-5p expression was decreased in CRC when compared to healthy controls and might be an effective diagnostic biomarker for CRC.
Conclusion: These data showed that miR-491-5p functioned as a tumor suppressor by targeting IGF2 in CRC, and miR-491-5p could serve as a potential diagnostic and prognostic biomarker for CRC.

Keywords: miR-491-5p, IGF2, colorectal cancer, proliferation, biomarker


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