Wang XL, Zhang L, Shang Q. Circular RNA hsa_circRNA_101996 modulates gastric cancer cell proliferation and apoptosis through the miR-577/HMGN5 axis. World J Gastrointest Oncol 2025; 17(5): 105933 [DOI: 10.4251/wjgo.v17.i5.105933]
Corresponding Author of This Article
Xiao-Lei Wang, PhD, Department of General Surgery, Xinxiang Central Hospital, No. 56 Jinsui Avenue, Xinxiang 453000, Henan Province, China. wangxl305@163.com
Research Domain of This Article
Biochemistry & Molecular Biology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
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: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. May 15, 2025; 17(5): 105933 Published online May 15, 2025. doi: 10.4251/wjgo.v17.i5.105933
Circular RNA hsa_circRNA_101996 modulates gastric cancer cell proliferation and apoptosis through the miR-577/HMGN5 axis
Xiao-Lei Wang, Lin Zhang, Qing Shang
Xiao-Lei Wang, Qing Shang, Department of General Surgery, Xinxiang Central Hospital, Xinxiang 453000, Henan Province, China
Lin Zhang, Department of Oncology, The First People's Hospital of Changshu, Suzhou 215501, Jiangsu Province, China
Author contributions: Wang XL designed the research study; Zhang L and Shang Q performed the research; all authors analyzed the data and wrote the manuscript and have read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Xinxiang Central Hospital Institutional Review Board (Approval No. 2023-227).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Ethical Committees of Xinxiang Central Hospital (Protocol No. 2024-KY-0723-001).
Conflict-of-interest statement: Dr. Wang has nothing to disclose.
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: Technical appendix, statistical code, and dataset available from the corresponding author at wangx1305@163.com.
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: Xiao-Lei Wang, PhD, Department of General Surgery, Xinxiang Central Hospital, No. 56 Jinsui Avenue, Xinxiang 453000, Henan Province, China. wangxl305@163.com
Received: February 11, 2025 Revised: March 19, 2025 Accepted: March 20, 2025 Published online: May 15, 2025 Processing time: 93 Days and 16.8 Hours
Abstract
BACKGROUND
Circular RNAs (circRNAs) are critical regulators in tumorigenesis, functioning as microRNA sponges or protein decoys. Although numerous circRNAs have been implicated in gastric cancer progression, the role of hsa_circRNA_101996 remains unclear. This study hypothesizes that hsa_circRNA_101996 promotes gastric cancer cell proliferation and apoptosis via the microRNA-577 (miR-577)/high mobility group nucleosome binding domain 5 (HMGN5) axis.
AIM
To investigate the role of hsa_circRNA_101996 in gastric cancer proliferation and apoptosis through the miR-577/HMGN5 axis.
METHODS
Forty-one paired gastric cancer tissues and adjacent non-cancerous tissues were analyzed. Differential circRNA expression was identified using GSE83521 and GSE89143 datasets. miR-577 and HMGN5 were predicted via CircInteractome and TargetScan. Functional experiments (MTT, colony formation, Western blot) and dual-luciferase reporter assays were performed in gastric cancer cell lines (OCUM-1, HSC-39). In vivo tumorigenesis was validated in nude mice. Statistical analysis included Student’s t-test and one-way ANOVA (P < 0.05).
RESULTS
Hsa_circRNA_101996 was significantly upregulated in gastric cancer tissues and cell lines compared to adjacent non-cancerous tissues (P < 0.05). Dual-luciferase reporter assays validated the interactions among hsa_circRNA_101996, miR-577, and HMGN5. In vitro, gastric cancer cells overexpressing hsa_circRNA_101996 showed significantly increased proliferation and decreased apoptosis compared to controls (P < 0.05). Cells transfected with miR-577 mimics exhibited reduced proliferation and increased apoptosis (P < 0.05). Co-transfection with hsa_circRNA_101996 or HMGN5 reversed the effects of miR-577 mimics. In vivo, hsa_circRNA_101996-overexpressing tumors showed increased volume and HMGN5 expression (P < 0.05).
CONCLUSION
Hsa_circRNA_101996 promotes gastric cancer progression by sponging miR-577 to upregulate HMGN5, suggesting a novel therapeutic target for gastric cancer.
Core Tip: This study reveals that circRNA_101996 promotes gastric cancer progression by sponging microRNA-577 (miR-577) to upregulate high mobility group nucleosome binding domain 5, thereby enhancing cell proliferation and inhibiting apoptosis. This study identifies a novel regulatory mechanism of circRNA_101996 in gastric cancer pathogenesis.
