miR-135b-5p/PDE3B Axis Regulates Gemcitabine Resistance in Pancreatic Cancer Through Epithelial-Mesenchymal Transition.

Abstract

Gemcitabine-based chemotherapy is an effective treatment for pancreatic cancer (PC), but gemcitabine resistance frequently compromises the therapeutic efficacy, resulting in clinical chemotherapeutic failure and a poor prognosis for patients. In this study, we investigated the mechanisms of gemcitabine chemoresistance in PC by examining the roles of microRNAs linked to gemcitabine resistance and their downstream signaling pathways. In vitro experiments were performed to alter miR-135b-5p levels in PC parental and drug-resistant cells to probe its function. miR-135b-5p targets PDE3B was confirmed by using RNA-seq technology to screen for gemcitabine-resistance-associated mRNAs in PC. A series of rescue experiments were performed after cotransfection, demonstrating that PDE3B could reverse miR-135b-5p-mediated chemoresistance and epithelial-mesenchymal transition (EMT). These findings indicate that the miR-135b-5p/PDE3B axis generates resistance by stimulating the EMT signaling pathway, which provides new insights into gemcitabine chemoresistance in PC.