中国肿瘤生物治疗杂志2025,Vol.32Issue(8):831-838,8.DOI:10.3872/j.issn.1007-385x.2025.08.006
circFSCN1通过miR-429/GPNMB轴影响胃癌细胞的恶性生物学行为
circFSCN1 regulates malignant behaviors of gastric cancer MGC803 cells via the miR-429/GPNMB axis
摘要
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.关键词
胃癌/circFSCN1/miR-429/非转移性黑色素蛋白B/增殖/迁移/侵袭Key words
gastric cancer/circular RNA fascin actin-bundling protein 1(circFSCN1)/microRNA-429(miR-429)/glycoprotein nonmetastatic melanoma protein B(GPNMB)/proliferation/migration/invasion分类
医药卫生引用本文复制引用
李超,王世卉,林洁,王凡珂,张蕊..circFSCN1通过miR-429/GPNMB轴影响胃癌细胞的恶性生物学行为[J].中国肿瘤生物治疗杂志,2025,32(8):831-838,8.基金项目
2022年政府资助临床医学优秀人才培养项目(No.LS202208) (No.LS202208)