Circular RNA hsa_circRNA_101996 modulates gastric cancer cell proliferation and apoptosis through the miR-577/HMGN5 axis

doi:10.4251/wjgo.v17.i5.105933

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World Journal of Gastrointestinal Oncology

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Basic Study

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.

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: 94 Days and 1.2 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.

Keywords: MicroRNA-577; Apoptosis; Proliferation; High mobility group nucleosome binding domain 5; CircRNA_101996; 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.