Copyright
©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
18β-glycyrrhetinic acid inhibits proliferation of gastric cancer cells through regulating the miR-345-5p/TGM2 signaling pathway
Xia Li, Xiao-Ling Ma, Yi Nan, Yu-Hua Du, Yi Yang, Dou-Dou Lu, Jun-Fei Zhang, Yan Chen, Lei Zhang, Yang Niu, Ling Yuan
Xia Li, Yu-Hua Du, Ling Yuan, College of Pharmacy, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Xiao-Ling Ma, Yi Nan, Yan Chen, Yang Niu, Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Yi Nan, Lei Zhang, Yang Niu, Key Laboratory of Hui Ethnic Medicine Modernization of Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Yi Yang, College of Basic Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Dou-Dou Lu, Jun-Fei Zhang, College of Clinical Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
Author contributions: Li X carried out most of the studies, and analyzed the data; Li X, Ma XL, and Du YH wrote the manuscript; Ma XL and Du YH carried out the chart-making work; Yang Y, Lu DD, and Zhang JF were responsible for network pharmacology analysis; Chen Y and Niu Y designed the study and revised the manuscript; Yuan L provided the conceptual and technical guidance as well as revised the manuscript critically for important intellectual content; and all authors have read and approved the manuscript.
Supported by the Ningxia Natural Science Foundation, No. 2022AAC03144.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Ningxia Medical University (No.2021-N0063).
Institutional animal care and use committee statement: The animal protocol was approved by the Institutional Animal Care and Use Committee of Ningxia Medical University (IACUC-NYLAC-2022-108).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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 (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, MD, PhD, Assistant Professor, College of Pharmacy, Ningxia Medical University, No. 1160 Shengli Street, Yinchuan 750004, Ningxia Hui Autonomous Region, China. 20080017@nxmu.edu.cn
Received: March 20, 2023
Peer-review started: March 20, 2023
First decision: April 10, 2023
Revised: April 24, 2023
Accepted: May 17, 2023
Article in press: May 17, 2023
Published online: June 21, 2023
ARTICLE HIGHLIGHTS
Research background
Gastric cancer (GC) is a common gastrointestinal malignancy worldwide. Based on the cancer-related mortality, the current prevention and treatment strategies for GC still show poor clinical results. Therefore, it is important to find effective drug treatment targets.
Research motivation
At present, the treatment of GC is mainly surgery, chemotherapy and radiotherapy, and the first-line treatment drugs are harmful to side effects.
Research objectives
The purpose of this study was to explore the molecular mechanism of 18β-glycyrrhetinic acid (18β-GRA) regulating the miR-345-5p/TGM2 signaling pathway to inhibit the proliferation of GC cells.
Research methods
The effects of 18β-GRA on GC cell phenotype and tumor growth in vivo were studied. TMT proteomic analysis and microRNAs (miRNAs) transcriptome analysis were used to screen for targets, and targeted connections were validated using a dual-luciferase report assay. Finally, the prediction was confirmed by experiment in vitro.
Research results
Our experiment confirmed that 18β-GRA inhibited GC cells growth both in vitro and in vivo, and MDC staining showed that 18β-GRA promoted GC cell autophagy. By TMT proteomic analysis and miRNAs transcriptomic analysis, we found that 18β-GRA down-regulates TGM2 expression and up-regulates miR-345-5p expression in GC cells. Subsequently, TGM2 was verified as the target of miR-345-5p by a dual-luciferase report assay. In 18β-GRA treated GC cells, the expressions of autophagy-related proteins TGM2 and p62 were significantly decreased, while the expressions of LC3II, ULK1 and AMPK were significantly increased. In addition, overexpression of miR-345-5p not only inhibited TGM2 expression, but also inhibited GC cell proliferation by promoting apoptosis and blocking cell cycle.
Research conclusions
These observations indicate that 18β-GRA can promote autophagy and inhibit GC cells proliferation via regulating the miR-345-5p/TGM2 signaling pathway.
Research perspectives
MiR-345-5p can be used for targeted therapy of GC, and can also be used as a new biomarker for GC.
