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<p>Gemcitabine (GEM) resistance undermines chemotherapy efficacy for pancreatic ductal adenocarcinoma (PDAC), resulting in poor prognosis. Long non-coding RNAs (LncRNAs) participate in various malignant tumors, including PDAC. However, their roles in GEM resistance require further elucidation. Here, we investigated the function of LINC01547 in PDAC progression and chemoresistance. LINC01547 was significantly upregulated in PDAC tissues and cell lines, and its high expression correlated with unfavorable patient outcomes. Silencing LINC01547 dramatically suppressed cellular proliferation, sphere formation capability and enhanced GEM sensitivity of PDAC cells both in vitro and in vivo experiments. Mechanistically, LINC01547 as a competing endogenous RNA that could regulate miR-34a-5p. RNA-sequencing and luciferase reporter analysis demonstrated that miR-34a-5p directly targets MYH9. Additionally, METTL3 mediated m6A modification boosted the RNA stabilization and upregulation of LINC01547. Taken together, these findings indicate that LINC01547 could promote tumor progression and gemcitabine resistance in PDAC via miR-34a-5p/MYH9 axis, highlighting LINC01547 as a potential biomarker and therapeutic target for overcoming chemoresistance in PDAC.</p> Graphical Abstract <p></p>

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m6A Modification-Mediated LINC01547 Promotes Pancreatic Cancer Growth and Gemcitabine Resistance Through miR-34a-5p/MYH9 Axis

  • 期刊论文

  • 发表日期：

    2025年10月5日

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  • Guangrui Lu,
  • Jianhua Gong,
  • Yue Chen,
  • Xiaosong Li,
  • Junyi Wang,
  • Jun Hu

摘要

Gemcitabine (GEM) resistance undermines chemotherapy efficacy for pancreatic ductal adenocarcinoma (PDAC), resulting in poor prognosis. Long non-coding RNAs (LncRNAs) participate in various malignant tumors, including PDAC. However, their roles in GEM resistance require further elucidation. Here, we investigated the function of LINC01547 in PDAC progression and chemoresistance. LINC01547 was significantly upregulated in PDAC tissues and cell lines, and its high expression correlated with unfavorable patient outcomes. Silencing LINC01547 dramatically suppressed cellular proliferation, sphere formation capability and enhanced GEM sensitivity of PDAC cells both in vitro and in vivo experiments. Mechanistically, LINC01547 as a competing endogenous RNA that could regulate miR-34a-5p. RNA-sequencing and luciferase reporter analysis demonstrated that miR-34a-5p directly targets MYH9. Additionally, METTL3 mediated m6A modification boosted the RNA stabilization and upregulation of LINC01547. Taken together, these findings indicate that LINC01547 could promote tumor progression and gemcitabine resistance in PDAC via miR-34a-5p/MYH9 axis, highlighting LINC01547 as a potential biomarker and therapeutic target for overcoming chemoresistance in PDAC.

Graphical Abstract