Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
LncRNA SNHG5 modulates cell proliferation and migration through the miR-92a-3p/BTG2 axis in gastric cancer by the PI3K/AKT pathway
Qi-Qi Mao, Mei-Lin Zhang, Liang Zhong, Xu-Dong Xu, Xin-Hai Wang, Du-Yi Pan, Fu-Sheng Zhou, Jia-Xin Huang, Xian-Guang Zhao, Jia-Jie Chen, Xiao-Yun Jiang, Xu Sun, Wei-Qun Ding
Qi-Qi Mao, Liang Zhong, Xu-Dong Xu, Du-Yi Pan, Fu-Sheng Zhou, Jia-Xin Huang, Xian-Guang Zhao, Jia-Jie Chen, Xiao-Yun Jiang, Xu Sun, Wei-Qun Ding, Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai 201907, China
Mei-Lin Zhang, Department of Pathology, Huashan Hospital, Fudan University, Shanghai 201907, China
Xin-Hai Wang, Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 201907, China
Co-first authors: Qi-Qi Mao and Mei-Lin Zhang.
Author contributions: Mao QQ and Zhang ML contributed equally to this work and should be considered co-first authors; Mao QQ, Zhang ML, and Zhong L designed the research study; Xu XD, Wang XH, Pan DY, and Zhou FS performed the research; Huang JX, Zhao XG, Chen JJ, Jiang XY, Sun X, and Ding WQ conducted experiments and analyzed the data; All authors contributed to editorial changes in the manuscript and read and approved the final manuscript.
Institutional review board statement: All patients provided written informed consent prior to any sample collection in accordance with the Declaration of Helsinki and institutional ethical policies. All tissue collections were done with protocols approved by the hospital's Institutional Review Board after a thorough ethics review, No. KY2022-0532.
Institutional animal care and use committee statement: The study carried out in accordance with Guidance on the operation of the Animals (Scientific Procedures) Act 1986 and associated guidelines, EU Directive 2010/63 for the protection of animals used for scientific purposes or the NIH (National Research Council) Guide for the Care and Use of Laboratory Animals (PDF). All procedures involving animals were reviewed and approved by the Animal Experimental Ethical Inspection of Guangzhou Miles Biosciences Co. Ltd., No. IACUC-MIS2023048. Huashan Hospital of Fudan University commissioned Guangzhou Miles Biosciences Co. Ltd. to carry out the Animal Ethical Review.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
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: Liang Zhong, Chief Physician, Department of Gastroenterology, Huashan Hospital, Fudan University, No. 12 Urumqi Middle Road, Shanghai 201907, China.
ifb422@yeah.net
Received: January 21, 2025
Revised: March 25, 2025
Accepted: June 16, 2025
Published online: August 15, 2025
Processing time: 208 Days and 11.3 Hours
BACKGROUND
Gastric cancer (GC) is a widespread malignancy and associated with high rates of morbidity and mortality worldwide.
AIM
To examine the functional role of long non-coding RNAs small nucleolar RNA host gene 5 (SNHG5) and its regulation of miR-92a-3p and B-cell translocation gene 2 (BTG2) in GC progression.
METHODS
Quantitative reverse transcription PCR and western blot analysis determined the expression of SNHG5, miR-92a-3p, and BTG2 in GC and adjacent non-neoplastic mucosa. Dual-luciferase assays demonstrated interactions of SNHG5 with miR-92a-3p and BTG2. AGS cells were transfected with SNHG5 overexpression and miR-92a-3p knockdown models. Various assays, including CCK-8, colony formation, scratch wound healing, and Transwell assays, were used to determine cell proliferation and migration. An experimental model of a xenograft mouse was used to determine in vivo tumor growth. At the same time histological changes were evaluated by hematoxylin and eosin staining, with western blot analysis used to evaluate signaling pathway protein expression.
RESULTS
BTG2 and SNHG5 were downregulated in GC tissues, and miR-92a-3p was upregulated. Overexpression of SNHG5 or knockdown of miR-92a-3p reduced GC cell proliferation and migration, and increased BTG2 expression while decreasing PI3K/AKT signaling activity. The dual-luciferase assays demonstrated direct binding of miR-92a-3p to SNHG5 and BTG2. Tumor volume and weight were significantly reduced in mice transplanted with AGS cells treated with miR-92a-3p inhibitor or SNHG5 overexpression compared with control AGS cells. Hematoxylin and eosin staining revealed that treated tumors exhibited degenerative characteristics, including irregular morphology and nucleolysis.
CONCLUSION
LncRNA SNHG5 inhibited GC cell growth and migration by modulating the PI3K/AKT pathway via the miR-92a-3p/BTG2 axis.
Core Tip: This study emphasized the role of long non-coding RNAs small nucleolar RNA host gene 5 (SNHG5) as a tumor suppression factor in gastric cancer (GC). SNHG5 acted as a competing endogenous RNA by reducing levels of miR-92a-3p, leading to increased levels of B-cell translocation gene 2, a tumor suppressor gene. This ultimately leads to the inhibition of GC cell proliferation and migration by inhibiting the PI3K/AKT signaling pathway. This is the first time that the SNHG5/miR-92a-3p/B-cell translocation gene 2 axis has been discovered to contribute to the progression of GC. This molecular understanding aids in providing an attractive target for therapy and will contribute to a framework of RNA-based approaches to diagnosing and treating GC.
