Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2019; 25(47): 6823-6834
Published online Dec 21, 2019. doi: 10.3748/wjg.v25.i47.6823
MiR-96-5p inhibition induces cell apoptosis in gastric adenocarcinoma
He-Ying Zhou, Chun-Qi Wu, En-Xu Bi
He-Ying Zhou, Chun-Qi Wu, Department of General Surgery, Jinan Seventh People's Hospital, Jinan 251400, Shandong Province, China
En-Xu Bi, Department of General Surgery, Qingdao West Coast New Area Central Hospital, Qingdao 266555, Shandong Province, China
Author contributions: Zhou HY designed the research; Chun QW performed the research; Chun QW and Bi EX analyzed the data and wrote the paper.
Institutional review board statement: This study was reviewed and approved by the Jinan Seventh People's Hospital Ethics Committee.
Informed consent statement: All patients in our study provided informed consent.
Conflict-of-interest statement: The authors declare no conflicts of interest.
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:
Corresponding author: En-Xu Bi, BSc, Chief Physician, Department of General Surgery, Qingdao West Coast New Area Central Hospital, No. 9 Huangpujiang Road, Qingdao Development Zone, Qingdao 266555, Shandong Province, China.
Telephone: +86-19026583164
Received: September 23, 2019
Peer-review started: September 23, 2019
First decision: November 4, 2019
Revised: November 15, 2019
Accepted: November 29, 2019
Article in press: November 29, 2019
Published online: December 21, 2019

Gastric adenocarcinoma (GAC) mortality rates have remained relatively changed over the past 30 years, and it continues to be one of the leading causes of cancer-related death.


To search for novel miRNAs related to GAC prognosis and further investigate the effect of miR-96-5p on MGC-803 cells.


The miRNA expression profile data of GAC based on The Cancer Genome Atlas were obtained and used to screen differently expressed miRNAs (DEMs) and DEMs related to GAC prognosis. Then, the expression of DEMs related to GAC prognosis was identified in GAC tumor samples and adjacent normal samples by qRT-PCR. The target gene, ZDHHC5, of miR-96-5p was predicted using TargetScan, miRTarBase, and miRDB databases and confirmed by luciferase reporter assay. Furthermore, MGC-803 cells were transfected with inhibitor NC, miR-96-5p inhibitor, si-ZDHHC5, or miR-96-5p inhibitor + si-ZDHHC5, and then cell apoptosis was detected by flow cytometry. The expression of ZDHHC5, Bcl-2, and COX-2 was detected using western blotting.


A total of 299 DEMs and 35 DEMs related to GAC prognosis were screened based on The Cancer Genome Atlas. Then compared with adjacent normal samples, the levels of miR-96-5p, miR-222-5p, and miR-652-5p were remarkably increased, while miR-125-5p, miR-145-3p, and miR-379-3p levels were reduced in GAC tumor samples (P < 0.01), which were consistent with bioinformatics analysis. Furthermore, ZDHHC5 was defined as a direct target gene of miR-96-5p. miR-96-5p inhibition increased the number of apoptotic cells as well as promoted the expression of ZDHHC5, Bcl-2, and COX-2 in MGC-803 cells (P < 0.01). After ZDHHC5 inhibition, the number of apoptotic cells and the expression of ZDHHC5, Bcl-2, and COX-2 were reduced. The addition of an miR-96-5p inhibitor partly reversed these effects (P < 0.01).


Our findings identified six miRNAs related to GAC prognosis and suggested that downregulated miR-96-5p might induce cell apoptosis via upregulating ZDHHC5 expression in MGC-803 cells.

Keywords: Gastric adenocarcinoma, Differently expressed miRNAs, Prognosis, MicroRNA-96-5p, Cell apoptosis, The Cancer Genome Atlas

Core tip: Gastric adenocarcinoma (GAC) is the most common malignant tumor. It is important to further reveal novel diagnostic and therapeutic methods as well as the underlying molecular mechanism of GAC. This study aimed to search for novel miRNAs related to GAC prognosis. Six miRNAs related to prognosis, including miR-96-5p, miR-125-5p, miR-145-3p, miR-222-5p, miR-379-3p, and miR-652-5p, were identified in GAC samples. Furthermore, downregulated miR-96-5p markedly induced cell apoptosis through targeting ZDHHC5. Current findings provide a potential molecular mechanism of miR-96-5p in GAC.