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<p>RNA-binding proteins (RBPs) are pivotal mediators of the alternative splicing (AS) machinery of pre-mRNA. Research has demonstrated that the AS process is significantly dysregulated and plays a crucial role in bladder cancer (BLCA). We conducted comprehensive screening and analysis of the TCGA-BLCA cohort, specifically focusing on genes with significant differences in expression levels between carcinoma and adjacent non-cancerous tissues. Among the 500 differentially expressed genes, 5 RNA-binding proteins were identified. Only the RNA-binding protein with multiple splicing (<i>RBPMS</i>) demonstrated a consistent downregulation in BLCA and was correlated with an unfavorable prognosis for affected patients. Subsequent experiments revealed that RBPMS exerted inhibitory effects on the epithelial-mesenchymal transition (EMT) pathway and the migratory potential of BLCA cells. RNA-Seq analysis identified <i>ANKRD10</i> as a key target mRNA regulated by RBPMS in BLCA. RBPMS depletion in BLCA cells resulted in AS of <i>ANKRD10</i> and increased ANKRD10-2 expression. ANKRD10-2 functioned as a transcriptional co-activator of MYC proteins, thereby augmenting their transcriptional activity. Furthermore, <i>ANKRD10</i>-2 knockdown significantly rescued the migration enhancement induced by RBPMS depletion in BLCA cells. Taken together, this study revealed a mechanism whereby RBPMS suppresses the migration and invasion of BLCA cells by attenuating MYC pathway activity via the AS of <i>ANKRD10</i>.</p>

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RBPMS inhibits bladder cancer metastasis by downregulating MYC pathway through alternative splicing of ANKRD10

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月5日

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  • Jingtian Yu,
  • Liang Chen,
  • Gang Wang,
  • Kaiyu Qian,
  • Hong Weng,
  • Zhonghua Yang,
  • Hang Zheng,
  • Mengxin Lu

摘要

RNA-binding proteins (RBPs) are pivotal mediators of the alternative splicing (AS) machinery of pre-mRNA. Research has demonstrated that the AS process is significantly dysregulated and plays a crucial role in bladder cancer (BLCA). We conducted comprehensive screening and analysis of the TCGA-BLCA cohort, specifically focusing on genes with significant differences in expression levels between carcinoma and adjacent non-cancerous tissues. Among the 500 differentially expressed genes, 5 RNA-binding proteins were identified. Only the RNA-binding protein with multiple splicing (RBPMS) demonstrated a consistent downregulation in BLCA and was correlated with an unfavorable prognosis for affected patients. Subsequent experiments revealed that RBPMS exerted inhibitory effects on the epithelial-mesenchymal transition (EMT) pathway and the migratory potential of BLCA cells. RNA-Seq analysis identified ANKRD10 as a key target mRNA regulated by RBPMS in BLCA. RBPMS depletion in BLCA cells resulted in AS of ANKRD10 and increased ANKRD10-2 expression. ANKRD10-2 functioned as a transcriptional co-activator of MYC proteins, thereby augmenting their transcriptional activity. Furthermore, ANKRD10-2 knockdown significantly rescued the migration enhancement induced by RBPMS depletion in BLCA cells. Taken together, this study revealed a mechanism whereby RBPMS suppresses the migration and invasion of BLCA cells by attenuating MYC pathway activity via the AS of ANKRD10.