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
ARTICLE HIGHLIGHTS
Research background

Colorectal cancer is the fourth most common cancer and the fifth most common cause of cancer-related death in China. Surgical resection followed by adjuvant chemotherapy, the most commonly used strategy for colorectal cancer management, has poor treatment response in some patients. Therefore, it is necessary to identify effective therapeutic targets to improve treatment and prognosis.

Research motivation

Long noncoding RNAs (lncRNAs), which may serve as novel therapeutic targets, are involved in the development and progression of human colorectal cancer. In our previous study, lncRNA RP4 was found to be dysregulated in colorectal cancer via microarray analysis. This indicated that this lncRNA may play an important role in colorectal cancer. Thus, in the present study, lncRNA RP4 was investigated to find out its role in colorectal cancer progression through an in vitro cell model and an in vivo xenograft model. Besides, the possible mechanisms in the regulation of lncRNA RP4 had not been well described.

Research objectives

To investigate the role of long noncoding (lnc)RNA RP4 in colorectal cancer, and to find out the possible mechanisms of the regulation.

Research methods

Cell counting kit-8 assay in vitro and xenograft tumor model in vivo were performed to evaluate the role of lncRNA RP4 in the regulation of proliferation. Annexin V/propidium iodide staining was performed to detect the role of lncRNA RP4 in apoptosis. qPCR and Western blot were performed to identify the relationship between lncRNA RP4 and SH3GLB1. And then, Western blot was done to analyse PI3K/Akt signaling pathway and autophagy pathway in the regulation.

Research results

Both cell counting kit-8 assay in vitro and xenograft tumor model in vivo showed that lncRNA RP4 could inhibit the proliferation and growth of colorectal cancer cells. lncRNA RP4 could promote early apoptosis. lncRNA RP4 was found to positively regulate SH3GLB1 expression, and correlation analyses further confirmed the existence of a significant correlation between lncRNA RP4 and SH3GLB1 expression. We also observed a positive regulatory effect of miR-7-5p on cell proliferation via the negative regulation of SH3GLB1.

Research conclusions

Our results demonstrate that lncRNA RP4 plays an important role in the progression of human colorectal cancer by functioning as a ceRNA to regulate the expression of SH3GLB1 through miR-7-5p sponge activity. The pleiotropic effects of lncRNA RP4 on colorectal cancer pathogenesis suggest that is has the potential to be a therapeutic target for colorectal cancer.

Research perspectives

This study suggests that the lncRNA intervention may be a promising treatment strategy for colorectal cancer. The future study might focus on the specific regulatory role of lncRNA RP4 in colorectal cancer in vivo, and the therapeutic effect of lncRNA RP4 needs to be validated in clinical practice.