<p>Papillary thyroid carcinoma (PTC), the most common thyroid malignancy, is characterized by a high incidence rate and unfavorable outcomes. The competing endogenous RNA (ceRNA) network is systemic and intricate, incorporating various non-coding RNAs, and offers new insights into the cancer pathogenesis. This study explored ceRNA-mediated pathways contributing to PTC pathogenesis. Datasets from GEO were analyzed to detect differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in PTC, which identified 49 DElncRNAs and two key genes, <i>RBM24</i> and <i>LIPI</i>. Then a total of 119 shared microRNAs (miRNAs) of them were predicted, leading to the construction of a comprehensive ceRNA regulatory network. Among these, <i>lncRNA CASC2</i>/<i>miR-193a-3p</i>/<i>RBM24</i> was identified as the core regulatory axis, by using the cytoHubba plugin in Cytoscape. Expression analysis using public datasets and clinical tissue samples revealed significant downregulation of <i>CASC2</i> and <i>RBM24</i>, alongside upregulation of <i>miR-193a-3p</i> in PTC. Dual-luciferase assays verified <i>CASC2</i>–<i>miR-193a-3p</i> and <i>miR-193a-3p</i>–<i>RBM24</i> binding. In IHH4 cells, <i>CASC2</i> knockdown promoted proliferation, migration, and invasion, whereas <i>miR-193a-3p</i> inhibition partly reversed the effects. The <i>RBM24</i> effect experiments demonstrated that reduced <i>RBM24</i> facilitated IHH4 progression. Xenograft models validated the expression patterns of <i>CASC2</i>, <i>miR-193a-3p</i>, and <i>RBM24</i> in vivo, showing that <i>CASC2</i> knockdown promoted tumor growth. This study is the first to identifies <i>lncRNA CASC2</i>/<i>miR-193a-3p</i>/<i>RBM24</i> as a critical modulator of PTC progression. By influencing proliferation, apoptosis, and motility, this axis sheds light on the molecular mechanisms of PTC and highlights the targets for therapeutic intervention.</p>

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Promoting mechanisms of papillary thyroid carcinoma by the LncRNA CASC2/miR-193a-3p/RBM24 axis

  • Dong Ou,
  • Yan Wu,
  • Youming Guo,
  • Xiaochi Hu,
  • Wei Liu,
  • Jinlong Huo

摘要

Papillary thyroid carcinoma (PTC), the most common thyroid malignancy, is characterized by a high incidence rate and unfavorable outcomes. The competing endogenous RNA (ceRNA) network is systemic and intricate, incorporating various non-coding RNAs, and offers new insights into the cancer pathogenesis. This study explored ceRNA-mediated pathways contributing to PTC pathogenesis. Datasets from GEO were analyzed to detect differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in PTC, which identified 49 DElncRNAs and two key genes, RBM24 and LIPI. Then a total of 119 shared microRNAs (miRNAs) of them were predicted, leading to the construction of a comprehensive ceRNA regulatory network. Among these, lncRNA CASC2/miR-193a-3p/RBM24 was identified as the core regulatory axis, by using the cytoHubba plugin in Cytoscape. Expression analysis using public datasets and clinical tissue samples revealed significant downregulation of CASC2 and RBM24, alongside upregulation of miR-193a-3p in PTC. Dual-luciferase assays verified CASC2miR-193a-3p and miR-193a-3pRBM24 binding. In IHH4 cells, CASC2 knockdown promoted proliferation, migration, and invasion, whereas miR-193a-3p inhibition partly reversed the effects. The RBM24 effect experiments demonstrated that reduced RBM24 facilitated IHH4 progression. Xenograft models validated the expression patterns of CASC2, miR-193a-3p, and RBM24 in vivo, showing that CASC2 knockdown promoted tumor growth. This study is the first to identifies lncRNA CASC2/miR-193a-3p/RBM24 as a critical modulator of PTC progression. By influencing proliferation, apoptosis, and motility, this axis sheds light on the molecular mechanisms of PTC and highlights the targets for therapeutic intervention.