Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 28, 2018; 24(4): 475-483
Published online Jan 28, 2018. doi: 10.3748/wjg.v24.i4.475
Overexpression of CREPT confers colorectal cancer sensitivity to fluorouracil
Yan-Shen Kuang, Yi Wang, Li-Dan Ding, Liu Yang, Ying Wang, Si-Han Liu, Bing-Tao Zhu, Xu-Ning Wang, Hong-Yi Liu, Jun Li, Zhi-Jie Chang, Yin-Yin Wang, Bao-Qing Jia
Yan-Shen Kuang, Xu-Ning Wang, Hong-Yi Liu, Bao-Qing Jia, General Surgery II Department, Chinese PLA General Hospital, Beijing 100853, China
Yi Wang, Li-Dan Ding, Liu Yang, Si-Han Liu, Bing-Tao Zhu, Zhi-Jie Chang, Yin-Yin Wang, State Key Laboratory of Membrane Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China
Jun Li, Institute of Immunology, PLA, The Third Military Medical University, Chongqing 400038, China
Author contributions: Kuang YS and Wang Y contributed equally to this work; Kuang YS performed the majority of experiments and analyzed the data; Wang Y contributed significantly to staining and analyzing of the immunohistochemistry experiments; Ding LD and Yang L helped perform the analysis with constructive discussions; Wang Y, Zhu BT and Li J helped perform the cell apoptosis detection; Wang XN and Liu HY contributed to obtaining the patients’ data; Jia BQ, Chang ZJ and Wang YY contributed to the conception and coordination of the study.
Supported by The Key Project Grant from the National Natural Science Foundation of China, No. 81372167, No. 81572729, No. 81402293, No. 81372372 and No. 81230044; and The National Key Research and Development Program of China, No. 2016YFA0500301.
Institutional review board statement: This study was approved by the Ethics Committee of the PLA General Hospital, Beijing, China. All patients involved in this study gave their informed consent for participation in the study.
Conflict-of-interest statement: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript titled “Overexpression of CREPT confers colorectal cancer sensitivity to fluorouracil”.
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: Bao-Qing Jia, MD, PhD, Chief Doctor, Professor, General Surgery II Department, Chinese PLA General Hospital, 28th, Haidian Dist., Beijing 100853, China. jiabaoqing@301hospital.com.cn
Telephone: +86-18910566719 Fax:+86-10-66937533
Received: October 22, 2017
Peer-review started: October 25, 2017
First decision: November 14, 2017
Revised: November 23, 2017
Accepted: November 28, 2017
Article in press: November 28, 2017
Published online: January 28, 2018
Abstract
AIM

To investigate expression of cell cycle-related and expression-elevated protein in tumor (CREPT) in colorectal cancer (CRC) and determine its prognostic value in response to 5-fluorouracil (5-FU).

METHODS

The relative expression of CREPT in CRC tumor samples was determined using immunohistochemistry. The protein content in cell lines was analyzed by immunoblotting. Cell viability was measured with the CCK-8 assay. Cell cycle and apoptosis analyses were performed with flow cytometry.

RESULTS

CREPT was overexpressed in CRC tissues and correlated with histological grade. Clinicopathological analysis indicated that CREPT was positively related to tumor progression. Exogenous expression of CREPT stimulated cell proliferation and accelerated the cell cycle. More importantly, high expression of CREPT sensitized CRC cells to 5-FU treatment. Furthermore, we demonstrated that 5-FU elicited significant apoptosis in CREPT-positive cells.

CONCLUSION

Aberrant overexpression of CREPT contributes to tumorigenesis of CRC by promoting cell proliferation and accelerating the cell cycle, and confers sensitivity to 5-FU. CREPT is a potential prognostic biomarker for 5-FU in CRC.

Keywords: CREPT, Colorectal cancer, 5-Fluorouracil, Apoptosis, Cell proliferation

Core tip: Cell cycle-related and expression-elevated protein in tumor (CREPT) is an oncogene that is preferentially expressed in diverse human tumors. Overexpression of CREPT promotes cell proliferation and tumorigenesis. However, the expression and mechanistic involvement of CREPT in colorectal cancer have not been fully investigated. Despite advances in clinical applications of 5-fluorouracil, drug resistance remains a significant limitation to its clinical use. A prognostic biomarker for administration of this drug is still urgently needed.