中国肿瘤生物治疗杂志2026，Vol.33Issue(8)：899-908,10.DOI:10.3872/j.issn.1007-385X.2026.08.010
RBM15通过TMBIM6/TGF-β/Smad轴促进宫颈癌细胞增殖、迁移及侵袭
RBM15 promotes proliferation,migration,and invasion of cervical cancer cells via the TMBIM6/TGF-β/Smad axis
摘要
Abstract
Objective:To investigate whether RNA binding motif protein 15(RBM15)promotes cervical cancer cell proliferation,migration,and invasion through the transmembrane Bax inhibitor motif-containing 6(TMBIM6)/TGF-β/Smad axis.Methods:Tumor tissues and adjacent tissues were collected from 82 cervical cancer patients who underwent surgical treatment at the Affiliated Zhangjiagang Hospital of Soochow University from January 2023 to January 2025.R was used to analyze RBM15 and TMBIM6 mRNA expression in The Cancer Genome Atlas(TCGA)database.Immunohistochemistry and Western blotting assays were used to detect RBM15 and TMBIM6 protein expression.Kaplan-Meier curves were used to analyze the associations of RBM15 and TMBIM6 mRNA expression with the prognosis of patients with cervical cancer.Cell Counting Kit-8(CCK-8),scratch,and Transwell invasion assays were used to evaluate the effects of RBM15 and TMBIM6 on cervical cancer cell proliferation,migration,and invasion.The sequence-based RNA adenosine methylation site predictor(SRAMP)was used to predict N6-methyladenosine(m6A)modification sites in TMBIM6 mRNA.RNA immunoprecipitation(RIP),RNA decay,and rescue assays were performed to investigate the interaction between RBM15 and TMBIM6 mRNA.Methylated RNA immunoprecipitation quantitative PCR(MeRIP-qPCR)was used to detect m6A enrichment in TMBIM6 mRNA.Western blotting assays were used to assess the effects of RBM15 and TMBIM6 on TGF-β/Smad pathway-related protein expression.Results:RBM15 and TMBIM6 mRNA expression levels in cervical cancer tissues were higher than those in adjacent noncancerous tissues(both P<0.05),and the positivity rates of RBM15 and TMBIM6 were higher in cancer tissues than in adjacent noncancerous tissues(both P<0.001).RBM15 and TMBIM6 protein expression levels in HeLa,MS-751,and SiHa cells were higher than those in Ect1/E6E7 cells(all P<0.05).The positivity rates of RBM15 and TMBIM6 in cervical cancer tissues at FIGO stages IB2-IIB were higher than those at stages IA-IB1(both P<0.05).The 5-year progression-free survival rates in the RBM15 and TMBIM6 high-expression groups were lower than those in their respective low-expression groups(both P<0.05).RBM15 mRNA expression was positively correlated with TMBIM6 mRNA expression in cervical cancer tissues(P<0.05).SRAMP predicted high-confidence m6A modification sites at positions 960,24876,and 25203 in TMBIM6 mRNA.RBM15 overexpression increased,whereas RBM15 knockdown decreased,TMBIM6 mRNA and protein expression in HeLa and SiHa cells(P<0.05).TMBIM6 mRNA was significantly enriched in RBM15 immunoprecipitates compared with the IgG group.MeRIP-qPCR showed significant m6A enrichment at positions 960,24876,and 25203 of TMBIM6 mRNA.RBM15 knockdown shortened the half-life and reduced the stability of TMBIM6 mRNA.RBM15 knockdown inhibited cervical cancer cell proliferation,migration,and invasion,whereas TMBIM6 overexpression reversed these effects.TMBIM6 overexpression increased TGF-β1,Smad2,and Smad3 protein expression,whereas RBM15 knockdown decreased their expression;TMBIM6 overexpression reversed the effects of RBM15 knockdown.Conclusion:The results suggest that RBM15 may increase TMBIM6 mRNA stability through m6A modification and activate the TGF-β/Smad pathway,thereby promoting cervical cancer cell proliferation,migration,and invasion.关键词
宫颈癌/RNA结合基序蛋白15/含跨膜Bax抑制基序蛋白6/TGF-β/Smad通路Key words
cervical cancer/RNA binding motif protein 15(RBM15)/transmembrane Bax inhibitor motif-containing 6(TMBIM6)/TGF-β/Smad pathway分类
医药卫生引用本文复制引用
郏柯,赵芳,黄海伟,张琳..RBM15通过TMBIM6/TGF-β/Smad轴促进宫颈癌细胞增殖、迁移及侵袭[J].中国肿瘤生物治疗杂志,2026,33(8):899-908,10.基金项目
江苏省妇幼健康科研项目(F202167) （F202167）
