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Archive > Volume 32 Issue 8 > 2025,32(8):831-838. DOI:10.3872/j.issn.1007-385X.2025.08.006 Prev Next
Basic Research
circFSCN1 regulates malignant behaviors of gastric cancer MGC803 cells via the miR-429/GPNMB axis
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Abstract:
[Abstract] Objective: To investigate the effects of circular RNA fascin actin-bundling protein 1 (circFSCN1) on the malignant biological behaviors of gastric cancer cells by regulating the microRNA-429 (miR-429)/glycoprotein nonmetastatic melanoma protein B (GPNMB) axis and its mechanisms. Methods: The gastric cancer tissues and corresponding para-cancerous tissues of 54 patients who underwent surgical resection at the First Hospital of Hebei Medical University between September 2022 and September 2023 were collected. The expressions of circFSCN1, miR-429 and GPNMB mRNA in gastric cancer tissues were detected by qPCR. Gastric cancer MGC803 cells were routinely cultured and divided into the control group, the sh-NC group, the sh-circFSCN1 group, the sh-circFSCN1+anti-NC group, and the sh-circFSCN1 + anti-miR-429 group. The expressions of circFSCN1, miR-429 and GPNMB mRNA in MGC803 cells of each group were detected by qPCR. The proliferation, migration, invasion and apoptosis of MGC803 cells in each group were detected by CCK-8 method, colony formation assay, Transwell assay and flow cytometry, respectively. Immunofluorescence was used to detect the expressions of GPNMB protein in cells of each group. WB assay was used to detect the expressions of PCNA, MMP-2, GPNMB and Cleaved Caspase-3 proteins in MGC803 cells of each group. Dual luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) assay were used to verify the binding regulatory relationship between circFSCN1 and miR-429, and between miR-429 and GPNMB. Results: circFSCN1 and GPNMB mRNA were both highly expressed in gastric cancer tissues (both P < 0.05), while miR-429 was lowly expressed (P < 0.05). Knockdown of circFSCN1 could promote the expression of miR-429 and inhibit the expression of GPNMB mRNA. Inhibition of miR-429 could promote the expression of GPNMB mRNA. Knockdown of circFSCN1 could significantly inhibit the proliferation, migration and invasion abilities of MGC803 cells and promote their apoptosis. Inhibition of miR-429 could partially reverse the effect of circFSCN1 knockdown. Knockdown of circFSCN1 could inhibit the expressions of PCNA, MMP-2 and GPNMB proteins in MGC803 cells and inhibit the expression of cleaved caspase-3 protein. There was a targeted binding and negative regulatory relationship between circFSCN1 and miR-429 and between miR-429 and GPNMB mRNA. Conclusion: Knocking down circFSCN1 inhibits the malignant biological behaviors of gastric cancer cells through the miR-429/GPNMB axis, indicating that circFSCN1 is a potential therapeutic target for gastric cancer.
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