<p>Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs that regulate gene expression and participate in various biological processes. circRNAs play a critical role in bladder cancer (BCa) development. circ_0001495, generated by back-splicing of exons 6 and 7 of the CCNB1 pre-mRNA, remains uncharacterized in BCa pathogenesis. This study explored the functional role and molecular mechanism of circ_0001495 in BCa. Using qRT-PCR, we detected circ_0001495 expression in BCa tissues and analyzed its correlation with clinical parameters. Sanger sequencing validated its circular structure, while fluorescence in situ hybridization (FISH) revealed predominant cytoplasmic localization. Bioinformatics analyses predicted its potential as a microRNA sponge, confirmed by dual-luciferase reporter assays showing direct binding to miR-1184. CCK-8, EdU incorporation, and colony formation assays evaluated cell proliferation and clonogenic capacity. Results showed that circ_0001495 correlated with tumor grade (<i>p</i> = 0.016) and was significantly upregulated in BCa tissues, exhibiting preliminary diagnostic potential for early-stage BCa (AUC = 0.739, sensitivity = 0.906, specificity = 0.562). Functional experiments demonstrated that circ_0001495 silencing inhibited BCa cell proliferation and colony formation. Mechanistically, circ_0001495 acted as a sponge for miR-1184, thereby activating key components of the MAPK signaling pathway (p-ERK, p-JUN, and p-JNK). Collectively, these findings indicate that circ_0001495 may serve as a potential diagnostic/prognostic biomarker for BCa and promotes tumor progression by activating the miR-1184/MAPK signaling axis.</p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

Circ_0001495 promotes bladder cancer progression by regulating miR-1184 via MAPK signaling pathway

  • Shoupeng Zhang,
  • Mingyuan Li,
  • Yubin Wu,
  • Yihan Kang,
  • Tianxiang Yang,
  • Bingzhen Han,
  • Jingyu Li,
  • Aijun Zhang

摘要

Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs that regulate gene expression and participate in various biological processes. circRNAs play a critical role in bladder cancer (BCa) development. circ_0001495, generated by back-splicing of exons 6 and 7 of the CCNB1 pre-mRNA, remains uncharacterized in BCa pathogenesis. This study explored the functional role and molecular mechanism of circ_0001495 in BCa. Using qRT-PCR, we detected circ_0001495 expression in BCa tissues and analyzed its correlation with clinical parameters. Sanger sequencing validated its circular structure, while fluorescence in situ hybridization (FISH) revealed predominant cytoplasmic localization. Bioinformatics analyses predicted its potential as a microRNA sponge, confirmed by dual-luciferase reporter assays showing direct binding to miR-1184. CCK-8, EdU incorporation, and colony formation assays evaluated cell proliferation and clonogenic capacity. Results showed that circ_0001495 correlated with tumor grade (p = 0.016) and was significantly upregulated in BCa tissues, exhibiting preliminary diagnostic potential for early-stage BCa (AUC = 0.739, sensitivity = 0.906, specificity = 0.562). Functional experiments demonstrated that circ_0001495 silencing inhibited BCa cell proliferation and colony formation. Mechanistically, circ_0001495 acted as a sponge for miR-1184, thereby activating key components of the MAPK signaling pathway (p-ERK, p-JUN, and p-JNK). Collectively, these findings indicate that circ_0001495 may serve as a potential diagnostic/prognostic biomarker for BCa and promotes tumor progression by activating the miR-1184/MAPK signaling axis.