Scholarlink

<p>Transforming growth factor (TGF)-β signaling is a key driver to induce epithelial-to-mesenchymal transition (EMT), a process that enhances cancer cell plasticity and metastatic potential. However, the role of circular RNAs (circRNAs) in TGF-β signaling remains largely unexplored. Here, we identify <i>circTGFBR2(3-6)</i>, a circRNA derived from <i>TGF-β receptor 2</i> (<i>TGFBR2</i>) pre-mRNA, as a critical enhancer of TGF-β/SMAD signaling in breast cancer cells. Depletion of <i>circTGFBR2(3-6)</i> inhibits TGF-β-induced EMT, cell migration, and in vivo extravasation of breast cancer cells. Mechanistically, <i>circTGFBR2(3-6)</i> acts as a scaffold that facilitates the interaction between the RNA-binding protein insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) and <i>TGF-β receptor 1</i> (<i>TGFBR1</i>) mRNA in an <i>N</i><sup>6</sup>-methyladenosine (m<sup>6</sup>A)-dependent manner, and thereby stabilizes <i>TGFBR1</i> mRNA and promotes its expression. Furthermore, <i>IGF2BP3</i> knockdown reduces <i>circTGFBR2(3-6)</i>-mediated enhancement of TGF-β/SMAD signaling, as well as TGF-β-induced EMT and cell migration. Our findings identify <i>circTGFBR2(3-6)</i> as a novel potentiator of TGF-β/SMAD signaling at the receptor level and highlight IGF2BP3 as a critical m<sup>6</sup>A reader that mediates <i>circTGFBR2(3-6)</i>-driven breast cancer cell plasticity.</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

circTGFBR2(3-6) acts as an assembly platform for RNA-binding protein IGF2BP3 and TGFBR1 mRNA to enhance breast cancer cell plasticity

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月27日

查看全文
  • Qian Wang,
  • Rayman T. N. Tjokrodirijo,
  • Hailiang Mei,
  • Peter A. van Veelen,
  • Peter ten Dijke,
  • Chuannan Fan

摘要

Transforming growth factor (TGF)-β signaling is a key driver to induce epithelial-to-mesenchymal transition (EMT), a process that enhances cancer cell plasticity and metastatic potential. However, the role of circular RNAs (circRNAs) in TGF-β signaling remains largely unexplored. Here, we identify circTGFBR2(3-6), a circRNA derived from TGF-β receptor 2 (TGFBR2) pre-mRNA, as a critical enhancer of TGF-β/SMAD signaling in breast cancer cells. Depletion of circTGFBR2(3-6) inhibits TGF-β-induced EMT, cell migration, and in vivo extravasation of breast cancer cells. Mechanistically, circTGFBR2(3-6) acts as a scaffold that facilitates the interaction between the RNA-binding protein insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) and TGF-β receptor 1 (TGFBR1) mRNA in an N6-methyladenosine (m6A)-dependent manner, and thereby stabilizes TGFBR1 mRNA and promotes its expression. Furthermore, IGF2BP3 knockdown reduces circTGFBR2(3-6)-mediated enhancement of TGF-β/SMAD signaling, as well as TGF-β-induced EMT and cell migration. Our findings identify circTGFBR2(3-6) as a novel potentiator of TGF-β/SMAD signaling at the receptor level and highlight IGF2BP3 as a critical m6A reader that mediates circTGFBR2(3-6)-driven breast cancer cell plasticity.