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MiR-27b-5p promotes gastric cancer progression by targeting CREBZF to regulate the STAT3 pathway
Fu-Chao Ma, Guan-Lan Zhang, Guo-Qiang Chen, Jing-Wen Ling, Yu-Feng Li, Bang-Teng Chi, Yu-Lu Tang, Wei Peng, Gang Chen, Dan-Ming Wei, Min-Hua Rong, Lian-Ying Ge
Fu-Chao Ma, Wei Peng, Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Guan-Lan Zhang, Guo-Qiang Chen, Jing-Wen Ling, Yu-Feng Li, Bang-Teng Chi, Yu-Lu Tang, Gang Chen, Dan-Ming Wei, Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Jing-Wen Ling, Department of Medical Information Engineering, School of Information and Management, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Min-Hua Rong, Department of Research, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Lian-Ying Ge, Department of Endoscopy, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Co-first authors: Fu-Chao Ma and Guan-Lan Zhang.
Co-corresponding authors: Min-Hua Rong and Lian-Ying Ge.
Author contributions: Ma FC and Zhang GL contributed equally as co-first authors; Ma FC, Zhang GL, Chen G, and Wei DM designed the research; Ma FC and Zhang GL collected clinical information and conducted the small RNA-sequencing and real-time quantitative reverse transcription polymerase chain reaction experiments; Ma FC, Zhang GL, Chen GQ, and Ling JW screened and processed the public small RNA sequencing datasets; Chen GQ, Ling JW, Peng W, and Tang YL analyzed the data; Ma FC, Zhang GL, Chi BT, Tang YL, and Peng W wrote the draft; Rong MH and Ge LY participated in manuscript revision and contributed equally as co-corresponding authors; all authors read and approved the final manuscript.
Supported by Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project, No. Z-A20220465; Guangxi Key Research and Development Plan, No. AB20297021; Guangxi Medical and Health Appropriate Technology Development and Promotion Application Project, No. S2022107; China Undergraduate Innovation and Entrepreneurship Training Program, No. S202310598074; and Future Academic Star of Guangxi Medical University, No. WLXSZX23109.
Institutional review board statement: This study was reviewed and approved by the Ethics Committees of Guangxi Medical University Cancer Hospital, No. KY2020148; Guilin People’s Hospital, No. 2020-102KY; and Youjiang Medical University, No. YYFY-LL-2024-005.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Ethics Committee of the Guangxi Medical University Animal Center, No. KY2020149.
Conflict-of-interest statement: All the 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: The data used to support the findings of this study are available from the corresponding author upon request.
Corresponding author: Lian-Ying Ge, Department of Endoscopy, Guangxi Medical University Cancer Hospital, No. 71 Hedi Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
gxgly@hotmail.com
Received: September 3, 2025
Revised: November 1, 2025
Accepted: December 23, 2025
Published online: March 15, 2026
Processing time: 190 Days and 21.6 Hours
BACKGROUND
Gastric cancer (GC) remains one of the most prevalent and deadly cancers globally. Recent advances in molecular biology show that microRNAs play essential roles in regulating gene expression and tumorigenesis. MiR-27b-5p has the potential to function as a biological indicator for GC progression alongside the target interaction of cAMP response element-binding protein zinc finger (CREBZF), but its exact role and mechanism in GC are currently unclear.
AIM
To explore the effect and potential mechanism of miR-27b-5p on the occurrence and development of GC by targeting CREBZF to regulate the signal transducer and activator of transcription signal transducer and activator of transcription 3 (STAT3) pathway.
METHODS
The regulatory roles of miR-27b-5p on CREBZF were validated through dual-luciferase reporter assays, real-time quantitative polymerase chain reaction, and western blotting to examine changes in the signaling axis. Cell models were created by overexpressing or knocking down miR-27b-5p and its target gene in lentivirus-transfected AGS and NCI-N87 cells. The changes in cellular proliferation were detected using cell counting kit-8 assays and flow cytometry, whereas cell migration was evaluated utilizing Transwell and wound healing experiments. The function of miR-27b-5p in the proliferation of GC cells was investigated in vivo employing a subcutaneous xenograft model in nude mice.
RESULTS
MiR-27b-5p showed higher expression levels in GC tissue compared to nearby non-cancerous tissue, while CREBZF displayed significant downregulation. Elevated miR-27b-5p levels inhibited CREBZF expression, as revealed by analyses of mRNA and protein, thereby promoting the proliferation and migratory capabilities of GC cell lines. Excess CREBZF counteracted this effect. Inhibition of miR-27b-5p diminished the proliferation and migration of GC cell lines, whereas CREBZF knockdown counteracted this outcome. Excessive miR-27b-5p expression altered the expression profile of genes in the STAT3 pathway as revealed by immunoblotting, including upregulation of STAT3, cellular myelocytomatosis oncogene, cyclin D1, B-cell lymphoma 2, and survivin, and downregulation of Bcl-2-associated X protein, Bcl-2-associated X protein/B-cell lymphoma 2, and CREBZF, which promoted proliferation and inhibited apoptosis of GC cells, and enhanced their migration ability. Overexpression of CREBZF counteracted these effects. Reducing expression of miR-27b-5p reversed these effects, while reducing expression of CREBZF negated this reversal. Animal experiments further proved that miR-27b-5p could facilitate tumorigenesis in nude mice, which was consistent with cell experiments.
CONCLUSION
MiR-27b-5p expression is elevated in GC and operates as an oncogene by targeting CREBZF to regulate the STAT3 pathway, promoting malignancy in GC. MiR-27b-5p is a potential therapeutic target.
Core Tip: Our findings provide preliminary evidence that reduction of miR-27b-5p restrains proliferation and migration of gastric cancer cells. Our investigation also indicates that elevated expression level of miR-27b-5p suppresses gene expression related to the signal transducer and activator of transcription 3 signaling pathway, mainly targeting cAMP response element-binding protein zinc finger. Specifically, this regulatory process includes upregulation of signal transducer and activator of transcription 3, cellular myelocytomatosis oncogene, cyclin D1, B-cell lymphoma 2, and survivin, as well as the downregulation of Bcl-2-associated X protein, Bcl-2-associated X protein/B-cell lymphoma 2 ratio, and cAMP response element-binding protein zinc finger. These molecular mechanisms enhance the proliferation of gastric cancer cells.
