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<p>Paclitaxel is a commonly used taxane in breast cancer (BCa) therapy. miRNA-targeted strategies aim to improve treatment efficacy by overcoming suboptimal responses and resistance. This study investigated the effect of miR-181a-3p silencing on paclitaxel sensitivity in triple-negative breast cancer (TNBC) and breast cancer stem cells (BCSCs). miR-181a-3p expression in BCa tissues and its target mRNAs were analyzed using computational tools. MDA-MB-231 (TNBC model), BCSC, and breast epithelial stem cell (BESC, healthy control) lines were used. RT-qPCR measured gene expression, while Annexin V-FITC and cell cycle kits assessed apoptosis and proliferation. Silencing was achieved via anti-miR-181a-3p transfection, and cells were treated with 10 µM paclitaxel for 48&#xa0;h. miR-181a-3p silencing significantly enhanced the apoptotic effect of paclitaxel on BCSCs and exhibited a pronounced apoptotic impact independently on these cells. No apoptotic effect was observed in MDA-MB-231 cells. In MDA-MB-231, miR-181a-3p silencing enhanced paclitaxel-induced G2/M arrest, but this effect was not seen in BCSCs. In BESCs, miR-181a-3p silencing decreased the apoptotic and G2/M arrest effects of paclitaxel. Five miR-181a-3p target genes (<i>CYCS</i>, <i>GSK3B</i>, <i>BAK1</i>, <i>IGF1R</i>, and <i>MAPK8</i>) highly expressed in BCa tissue and implicated in key signaling pathways were computationally identified. Although all were theoretically expected to increase upon silencing, expression changes varied. In BCSCs, apoptotic genes BAK1 and CYCS were upregulated, while proliferative genes IGF1R, MAPK8, and GSK3B were downregulated, consistent with other data. In conclusion, miR-181a-3p modulates apoptotic and cell cycle responses to paclitaxel, positioning it as a promising therapeutic option and biomarker, particularly for addressing BCSC-related resistance and relapse.</p>

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Defeating miR-181a-3p may potentiate the effect of paclitaxel on G2/M arrest in breast cancer stem cells

  • 期刊论文

  • 发表日期：

    2025年11月5日

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  • Aycan Asik,
  • Bakiye Goker Bagca,
  • Neslihan Pinar Ozates,
  • Roya Gasimli,
  • Cigir Biray Avci,
  • Cumhur Gunduz

摘要

Paclitaxel is a commonly used taxane in breast cancer (BCa) therapy. miRNA-targeted strategies aim to improve treatment efficacy by overcoming suboptimal responses and resistance. This study investigated the effect of miR-181a-3p silencing on paclitaxel sensitivity in triple-negative breast cancer (TNBC) and breast cancer stem cells (BCSCs). miR-181a-3p expression in BCa tissues and its target mRNAs were analyzed using computational tools. MDA-MB-231 (TNBC model), BCSC, and breast epithelial stem cell (BESC, healthy control) lines were used. RT-qPCR measured gene expression, while Annexin V-FITC and cell cycle kits assessed apoptosis and proliferation. Silencing was achieved via anti-miR-181a-3p transfection, and cells were treated with 10 µM paclitaxel for 48 h. miR-181a-3p silencing significantly enhanced the apoptotic effect of paclitaxel on BCSCs and exhibited a pronounced apoptotic impact independently on these cells. No apoptotic effect was observed in MDA-MB-231 cells. In MDA-MB-231, miR-181a-3p silencing enhanced paclitaxel-induced G2/M arrest, but this effect was not seen in BCSCs. In BESCs, miR-181a-3p silencing decreased the apoptotic and G2/M arrest effects of paclitaxel. Five miR-181a-3p target genes (CYCS, GSK3B, BAK1, IGF1R, and MAPK8) highly expressed in BCa tissue and implicated in key signaling pathways were computationally identified. Although all were theoretically expected to increase upon silencing, expression changes varied. In BCSCs, apoptotic genes BAK1 and CYCS were upregulated, while proliferative genes IGF1R, MAPK8, and GSK3B were downregulated, consistent with other data. In conclusion, miR-181a-3p modulates apoptotic and cell cycle responses to paclitaxel, positioning it as a promising therapeutic option and biomarker, particularly for addressing BCSC-related resistance and relapse.