Downregulation of miR-301a-3p sensitizes pancreatic cancer cells to gemcitabine treatment via PTEN.

Background: We previously showed that miR-301a-3p affects the invasion and migration abilities of pancreatic cancer cells. Here, we explore the role of miR-301a-3p in chemoresistance, which represents a major obstacle in cancer treatment. Methods: We tested the effects of miR-301a-3p ongemcitabine resistance in cytotoxicity assays in vitro and in vivo. We used quantitative real-time PCR (qRT-PCR) to measure miR-301a-3p expression in wild-type and gemcitabine-resistant pancreatic cancer cells. We performed Western blot, qRT-PCR, and luciferase and rescue assays to confirm the direct target of miR-301a-3p. Results: The overexpression and inhibition of miR301a-3p promoted and reversed, respectively, gemcitabine resistance in pancreatic cancer cells in vitro. The role of miR-301-3p in chemoresistance was dependent on PTEN. The suppression of miR-301-3p expression sensitized pancreatic cancer cells to gemcitabine chemotherapy in a xenograft mouse model. Conclusion: MiR-301a-3p confers resistance to gemcitabine by regulating the expression of PTEN. The co-delivery of miR-301a-3p and gemcitabine might be an effective therapeutic regimen for patients with pancreatic cancer.