The Influence of MicroRNA-31 on Oxidative Stress and Radiosensitivity in Pancreatic Ductal Adenocarcinoma

Cells. 2022 Jul 25;11(15):2294. doi: 10.3390/cells11152294.

Abstract

Radioresistance remains a significant challenge in treating pancreatic ductal adenocarcinoma (PDAC), contributing to the poor survival rates of this cancer. MicroRNAs (miRs) are small non-coding RNA molecules that may play an essential role in regulating radioresistance by altering the levels of oxidative stress. In this study, we investigated the role and potential mechanisms linking miR-31 to PDAC radioresistance. A pCMV-miR vector containing a miR-31 mimic was stably expressed into a miR-31-deficient PDAC cell line, BxPC-3. Additionally, a pmiRZip lentivector suppressing miR-31 was stably expressed in a miR-31 abundant PDAC cell line, Panc-1. Clonogenic assays were conducted to explore the role of miR-31 manipulation on radiosensitivity. Fluorometric ROS assays were performed to quantify ROS levels. The expression of potential miR-31 targets was measured by Western blot analysis. It was found that the manipulation of miR-31 altered the radiosensitivity in PDAC cells by regulating oxidative stress. Using online bioinformatics tools, we identified the 3'UTR of GPx8 as a predicted target of miR-31. Our study demonstrates, for the first time, that manipulating miR-31 alters GPx8 expression, regulating ROS detoxification and promoting either a radioresistant or radiosensitive phenotype. MiR-31 may represent a promising therapeutic target for altering radiosensitivity in PDAC cells.

Keywords: DNA damage response; glutathione peroxidase; microRNA; oxidative stress; pancreatic ductal adenocarcinoma; radiotherapy; reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Pancreatic Ductal* / genetics
  • Carcinoma, Pancreatic Ductal* / metabolism
  • Carcinoma, Pancreatic Ductal* / radiotherapy
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • Oxidative Stress / genetics
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / metabolism
  • Pancreatic Neoplasms* / radiotherapy
  • Peroxidases / metabolism
  • Radiation Tolerance / genetics
  • Reactive Oxygen Species / metabolism

Substances

  • MIRN31 microRNA, human
  • MicroRNAs
  • Reactive Oxygen Species
  • GPX8 protein, human
  • Peroxidases

Grants and funding

This research was funded by a Provost’s Ph.D. Project Award from Trinity College Dublin.