Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2018; 24(9): 1004-1012
Published online Mar 7, 2018. doi: 10.3748/wjg.v24.i9.1004
Long noncoding RNA RP4 functions as a competing endogenous RNA through miR-7-5p sponge activity in colorectal cancer
Mu-Lin Liu, Qiao Zhang, Xiao Yuan, Long Jin, Li-Li Wang, Tao-Tao Fang, Wen-Bin Wang
Mu-Lin Liu, Long Jin, Li-Li Wang, Tao-Tao Fang, Department of Gastrointestinal Surgery, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, Anhui Province, China
Qiao Zhang, Department of General Surgery, the First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453100, Henan Province, China
Xiao Yuan, Wen-Bin Wang, Department of General Surgery, the Fourth Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China
Author contributions: Liu ML, Zhang Q and Yuan X contributed equally to this work; Liu ML and Zhang Q conceived the study and participated in its design and coordination; Yuan X drafted and revised the manuscript; Jin L helped with the statistical analysis; Wang LL and Fang TT performed the experiments; Wang WB conceived the study and revised the manuscript; all authors read and approved the final manuscript.
Supported by Scientific Research Foundation of Anhui Education Department, No. KJ2017A219 to Liu ML; Scientific Research Foundation of Academic Leader of Anhui Province, No. 2016H105 to Liu ML; Education Talent Foundation of Universities of Anhui Education Department, No. gxbjZD2016070 to Liu ML; National Natural Science Foundation of China, No. 81500373 to Wang WB; and Natural Science Foundation of Anhui Province, No. 1608085MH193 to Wang WB.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Bengbu Medical College.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of SHRM.
Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study.
Data sharing statement: The datasets supporting the conclusions of this article are included within the article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Wen-Bin Wang, PhD, Doctor, Professor, Department of General Surgery, the Fourth Affiliated Hospital of Anhui Medical University, No. 372, Tunxi Road, Hefei 230022, Anhui Province, China. surdoctor@163.com
Telephone: +86-551-62879386 Fax:+86-552-3070260
Received: November 15, 2017
Peer-review started: November 16, 2017
First decision: December 20, 2017
Revised: December 26, 2017
Accepted: January 16, 2018
Article in press: January 16, 2018
Published online: March 7, 2018
Processing time: 109 Days and 20.8 Hours
Abstract
AIM

To investigate the role of long noncoding RNA (lncRNA) RP4 in colorectal cancer.

METHODS

Lentivirus-mediated lncRNA RP4 overexpression and knockdown were performed in the colorectal cancer cell line SW480. Cell proliferation, tumor growth, and early apoptosis were evaluated by a cell counting kit-8 assay, an in vivo xenograft tumor model, and annexin V/propidium iodide staining, respectively. Analysis of the lncRNA RP4 mechanism involved assessment of the association of its expression with miR-7-5p and the SH3GLB1 gene. Western blot analysis was also performed to assess the effect of lncRNA RP4 on the autophagy-mediated cell death pathway and phosphatidylinositol-3-kinase (PI3K)/Akt signaling.

RESULTS

Cell proliferation, tumor growth, and early apoptosis in SW480 cells were negatively regulated by lncRNA RP4. Functional experiments indicated that lncRNA RP4 directly upregulated SH3GLB1 expression by acting as a competing endogenous RNA (ceRNA) for miR-7-5p. This interaction led to activation of the autophagy-mediated cell death pathway and de-repression of PI3K and Akt phosphorylation in colorectal cancer cells in vivo.

CONCLUSION

Our results demonstrated that lncRNA RP4 is a ceRNA that plays an important role in the pathogenesis of colorectal cancer, and could be a potential therapeutic target for colorectal cancer treatment.

Keywords: Colorectal cancer; Long noncoding RNA RP4; SH3GLB1; miR-7-5p; Competing endogenous RNA

Core tip: In the present study, we investigated the role of long noncoding RNA (lncRNA) RP4 in colorectal cancer using an in vivo cell model and an in vivo xenograft model. Mechanistic analysis suggested that lncRNA RP4 functions in colorectal cancer pathogenesis as a competing endogenous RNA that regulates SH3GLB1 expression by acting as a sponge for miR-7-5p. It could also serve as a potential therapeutic target for colorectal cancer treatment.