Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2017; 23(13): 2337-2345
Published online Apr 7, 2017. doi: 10.3748/wjg.v23.i13.2337
MicroRNA-145 exerts tumor-suppressive and chemo-resistance lowering effects by targeting CD44 in gastric cancer
Jian-Feng Zeng, Xiao-Qiu Ma, Lin-Pei Wang, Wei Wang
Jian-Feng Zeng, Lin-Pei Wang, Wei Wang, Department of General Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian Province, China
Xiao-Qiu Ma, Department of Medical Oncology, The 180th Hospital of the People’s Liberation Army, Quanzhou 362000, Fujian Province, China
Author contributions: Wang LP and Wang W contributed to the study design. Zeng JF and Ma XQ performed the majority of experiments, collected the data, and wrote the manuscript; all authors approved the final manuscript for publication.
Supported by Quanzhou excellent personnel training, No. 10A16; Natural Science Foundation of Fujian Province, No. JA08084; and Fujian Medical University, No. 092D014.
Institutional review board statement: This study was reviewed and approved by The Second Affiliated Hospital of Fujian Medical University Institutional Review Board, Quanzhou, China.
Conflict-of-interest statement: The authors declare that there are no potential conflicts of interest relevant to this article.
Data sharing statement: No additional data are available.
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: Dr. Wei Wang, Department of General Surgery, The Second Affiliated Hospital of Fujian Medical University, Zhongshanbei Road 34, Quanzhou 362000, Fujian Province, China. wanglinpei@126.com
Telephone: +86-595-22780153 Fax: +86-595-22780153
Received: October 10, 2016
Peer-review started: October 12, 2016
First decision: December 2, 2016
Revised: January 9, 2017
Accepted: February 8, 2017
Article in press: February 8, 2017
Published online: April 7, 2017
Abstract
AIM

To determine the potential roles of CD4 and microRNA (miR)-145 in gastric cancer.

METHODS

The levels of CD44 and miR-145 were determined in gastric cancer cells. Quantitative real-time polymerase chain reaction was used to measure to the level of CD44 mRNA. A luciferase reporter assay and western blotting were performed to examine the effect of miR-145 on CD44 expression. Tumor sphere and MTT assays were carried out to evaluate the self-renewal and chemo-resistance properties of gastric cancer cells.

RESULTS

The expression of CD44 was greatly increased and miR-145 was decreased in gastric cancer cells that were highly enriched in cancer stem cells (CSCs). The results demonstrated that miR-145 regulated CD44 by targeting directly the CD44 3’-untranslated region (3’-UTR). In gastric cancer cells, overexpression of miR-145 repressed the activity of the CD44 3’-UTR, and disruption of miR-145/CD44 3’-UTR interactions abrogated the silencing effects. In addition, miR-145 inhibition stimulated CD44 3’-UTR activity and disruption of miR-145/CD44 3’-UTR interactions abrogated this stimulatory effect. Enforced CD44 expression greatly increased tumor sphere formation and chemo-resistance in gastric cancer cells. Furthermore, the inhibition of CSCs and the chemo-sensitivity of gastric cancer cells treated with miR-145 were significantly abrogated by overexpression of CD44.

CONCLUSION

miR-145 targeting of CD44 plays critical roles in the regulation of tumor growth and chemo-resistance in gastric cancer.

Keywords: miR-145, CD44, Gastric cancer stem cells, Chemo-resistance

Core tip: The levels of CD44 and miR-145 are related strongly to stemness properties in gastric cancer. The aim of this investigation was to determine the underlying molecular mechanism involved in this relationship. The findings demonstrated that miR-145 regulates CD44 expression by directly targeting its 3’-untranslated region, which might play a critical role in the regulation of tumor growth and chemo-resistance in gastric cancer.