m6A modification-mediated LINC01547 promotes pancreatic cancer growth and gemcitabine sensitivity through miR-34a-5p/MYH9 axis

Gemcitabine (GEM) resistance reduces 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 biological mechanism in GEM resistance of PDAC remains further exploration. This study aims to reveal the role of LINC01547 in monitoring and chemotherapy of PDAC. LINC01547 was significantly upregulated in PDAC tissues and cell lines, which was negatively correlated with patient prognosis. 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 an endogenous competing RNA could regulate miR-34a-5p. RNA-sequencing and luciferase reporter analysis demonstrated that miR-34a-5p targets MYH9. Additionally, METTL3 mediated m6A modification boosted the RNA stabilization and upregulation of LINC01547. Taken together, LINC01547 could promote tumor progression and gemcitabine resistance in PDAC by regulating miR-34a-5p/MYH9 axis, providing a novel strategy and therapeutic target for patients with chemoresistance of PDAC.