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©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
MiR-204-3p overexpression inhibits gastric carcinoma cell proliferation by inhibiting the MAPK pathway and RIP1/MLK1 necroptosis pathway to promote apoptosis
Xia Li, Joanna J Tibenda, Yi Nan, Shi-Cong Huang, Na Ning, Guo-Qing Chen, Yu-Hua Du, Ya-Ting Yang, Fan-Di Meng, Ling Yuan
Xia Li, Joanna J Tibenda, Shi-Cong Huang, Na Ning, Guo-Qing Chen, Yu-Hua Du, Ling Yuan, College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Xia Li, Ningxia Chinese Medicine Reserch Center, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Yi Nan, Fan-Di Meng, Key Laboratory of Hui Ethnic Medicine Modernization of Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Yi Nan, Ya-Ting Yang, Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Author contributions: Li X carried out most of the studies, analyzed the data, and wrote the manuscript; Nan Y designed the study and revised the manuscript; Tibenda JJ, Du YH and Huang SC wrote the manuscript, and conducted the chart-making work; Ning N and Chen GQ were responsible for the total transcriptomic; Yang YT and Meng FD performed parts of the in vivo and in vitro experiments, and conducted statistical analysis of the data; Yuan L and Nan Y provided the conceptual and technical guidance and revised the manuscript critically for important intellectual content; all authors have read and approved the manuscript.
Supported by Ningxia Natural Science Foundation, No. 2022AAC03144.
Institutional review board statement: This manuscript does not involve human experiments.
Institutional animal care and use committee statement: The animal study protocol was approved by the Institutional Animal Care and Use Committee of Ningxia Medical University, No. IACUC-NYLAC-2022-251.
Conflict-of-interest statement: All authors declare no financial or commercial conflict of interest for this article. This article was published during the period of Ling Yuan granted "Young Scholars of Western China"(Class A)_West Light Foundation of the Chinese Academy of Sciences.
Data sharing statement: All data generated or analyzed during this study are included in this paper, and further inquiries can be directed to the corresponding author (E-mail: 20080017@nxmu.edu.cn).
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Ling Yuan, PhD, Professor, College of Pharmacy, Ningxia Medical University, No. 1160 Shengli Street, Yinchuan 750004, Ningxia Hui Autonomous Region, China. 20080017@nxmu.edu.cn
Received: May 6, 2023
Peer-review started: May 6, 2023
First decision: May 17, 2023
Revised: May 24, 2023
Accepted: July 5, 2023
Article in press: July 5, 2023
Published online: August 7, 2023
BACKGROUND
Gastric carcinoma (GC) is the third most frequent cause of cancer-related death, highlighting the pressing need for novel clinical treatment options. In this regard, microRNAs (miRNAs) have emerged as a promising therapeutic strategy. Studies have shown that miRNAs can regulate related signaling pathways, acting as tumor suppressors or tumor promoters.
AIM
To explore the effect of miR-204-3p on GC cells.
METHODS
We measured the expression levels of miR-204-3p in GC cells using quantitative real-time polymerase chain reaction, followed by the delivery of miR-204-3p overexpression and miR-204-3p knockdown vectors into GC cells. CCK-8 was used to detect the effect of miR-204-3p on the proliferation of GC cells, and the colony formation ability of GC cells was detected by the clonal formation assay. The effects of miR-204-3p on GC cell cycle and apoptosis were detected by flow cytometry. The BABL/c nude mouse subcutaneous tumor model using MKN-45 cells was constructed to verify the effect of miR-204-3p on the tumorigenicity of GC cells. Furthermore, the study investigated the effects of miR-204-3p on various proteins related to the MAPK signaling pathway, necroptosis signaling pathway and apoptosis signaling pathway on GC cells using Western blot techniques.
RESULTS
Firstly, we found that the expression of miR-204-3p in GC was low. When treated with the lentivirus overexpression vector, miR-204-3p expression significantly increased, but the lentivirus knockout vector had no significant effect on miR-204-3p. In vitro experiments confirmed that miR-204-3p overexpression inhibited GC cell viability, promoted cell apoptosis, blocked the cell cycle, and inhibited colony formation ability. In vivo animal experiments confirmed that miR-204-3p overexpression inhibited subcutaneous tumorigenesis ability in BABL/c nude mice. Simultaneously, our results verified that miR-204-3p overexpression can inhibit GC cell proliferation by inhibiting protein expression levels of KRAS and p-ERK1/2 in the MAPK pathway, as well as inhibiting protein expression levels of p-RIP1 and p-MLK1 in the necroptosis pathway to promote the BCL-2/BAX/Caspase-3 apoptosis pathway.
CONCLUSION
MiR-204-3p overexpression inhibited GC cell proliferation by inhibiting the MAPK pathway and necroptosis pathway to promote apoptosis of GC cells. Thus, miR-204-3p may represent a new potential therapeutic target for GC.
Core Tip: Gastric carcinoma (GC) is a global health problem that seriously endangers human life; therefore, it is important to identify effective treatment targets. In this regard, microRNAs (miRNAs) have emerged as a promising therapeutic strategy. Studies have shown that miRNAs regulated signaling pathways, acting as tumor suppressors or tumor promoters. In this study, we first verified the inhibitory effect of miR-204-3p overexpression on GC cells through in vitro and in vivo experiments. Simultaneously, miR-204-3p overexpression induced GC cell apoptosis by inhibiting the MAPK pathway and the necroptosis pathway. Thus, miR-204-3p may represent a new potential therapeutic target for GC.
