Case Control Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 7, 2020; 26(5): 499-513
Published online Feb 7, 2020. doi: 10.3748/wjg.v26.i5.499
Upregulation of miR-34c after silencing E2F transcription factor 1 inhibits paclitaxel combined with cisplatin resistance in gastric cancer cells
Hong Zheng, Jin-Jing Wang, Xiao-Rong Yang, Yong-Lin Yu
Hong Zheng, Jin-Jing Wang, Xiao-Rong Yang, Yong-Lin Yu, Department of Pathology, the Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
Author contributions: Zheng H designed the research; Wang JJ performed the research; Yang XR and Yu YL analyzed the data and wrote the paper.
Institutional review board statement: The study was approved by the Ethics Committee of the Affiliated Hospital of Zunyi Medical University (Guizhou, China).
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Hong Zheng, PhD, Chief Physician, Department of Pathology, the Affiliated Hospital of Zunyi Medical University, No. 149, Dalian Road, Zunyi 563003, Guizhou Province, China.
Received: November 5, 2019
Peer-review started: November 5, 2019
First decision: December 7, 2019
Revised: December 13, 2019
Accepted: January 2, 2020
Article in press: January 3, 2020
Published online: February 7, 2020

MicroRNA 34c (miR-34c) has been reported to be associated with malignant types of cancer, however, it remains unknown whether miR-34c is involved in chemoresistance in gastric cancer (GC).


To investigate the effect of miR-34c and its upstream transcription factor E2F1 on paclitaxel combined with cisplatin resistance in GC cells.


Paired GC tissues and adjacent normal tissues were randomly sampled from 74 GC patients. miR-34c and E2F1 were detected by real-time quantitative PCR (qPCR) and Western blot. In addition, the drug resistance of GC cells to paclitaxel and cisplatin was induced by concentration gradient increasing methods, and changes in miR-34c and E2F1 during this process were measured. Furthermore, E2F1 and miR-34c overexpression or underexpression vectors were constructed and transfected into drug-resistant GC cells. MTT was employed to test the sensitivity of cells to paclitaxel combined with cisplatin, qPCR was adopted to detect the expression of miR-34c, Western blot was applied to detect the expression levels of E2F1, drug resistance-related proteins and apoptosis-related proteins, and flow cytometry was used for the determination of cell apoptosis and cell cycle status.


E2F1 was overexpressed while miR-34c was underexpressed in GC. After inducing GC cells to be resistant to paclitaxel and cisplatin, E2F1 expression increased while miR-34c expression decreased. Both silencing E2F1 and over-expressing miR-34c could increase the sensitivity of drug-resistant GC cells to paclitaxel combined with cisplatin, promote cell apoptosis and inhibit cell proliferation. Among which, silencing E2F1 could reduce the expression of drug resistance-related proteins and apoptosis-related proteins, while over-expression of miR-34c could upregulate the expression of apoptosis-related proteins without affecting the expression of MDR-1, MRP and other drug resistance-related proteins. Rescue experiments demonstrated that inhibiting miR-34c could significantly weaken the sensitization of drug resistant cells, and Si E2F1 to paclitaxel combined with cisplatin.


E2F1 inhibits miR-34c to promote the proliferation of GC cells and enhance the resistance to paclitaxel combined with cisplatin, and silencing E2F1 is conducive to improving the efficacy of paclitaxel combined with cisplatin in GC cells.

Keywords: E2F transcription factor 1, MicroRNA 34c, Gastric cancer, Paclitaxel combined with cisplatin resistance

Core tip: Gastric cancer (GC) is one of the most common types of cancer. The molecular mechanism of GC is intricate, and understanding the molecular mechanism of drug resistance is helpful for improving the efficacy of chemotherapy. The mutual binding of miRNAs and transcription factors is closely related to cancer occurrence. In this study, we found that E2F transcription factor 1 inhibited miR-34c transcription to both promote GC cell proliferation as well as enhance the resistance of paclitaxel combined with cisplatin. Therefore, silencing the expression of E2F transcription factor 1 in GC cells could improve the efficacy of paclitaxel combined with cisplatin.