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miR-125a-3p is responsible for chemosensitivity in PDAC by inhibiting epithelial-mesenchymal transition via Fyn

Guodong Liu1, Liandong Ji1, Mujing Ke2

  • 1Department of Pancreatic Biliary Surgery, Xiangya Hospital, Central South University, Changsha, 410008, PR China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|July 11, 2018
PubMed
Abstract

Insights

This study reveals that miR-125a-3p enhances pancreatic cancer chemoresistance by targeting Fyn and inhibiting EMT. This offers a new therapeutic approach for pancreatic ductal adenocarcinoma (PDAC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with significant mortality due to chemoresistance.
  • The role of miR-125a-3p in PDAC and its impact on chemosensitivity remained largely unknown.

Purpose of the Study:

  • To investigate the function of miR-125a-3p in chemoresistance and epithelial-mesenchymal transition (EMT) in PDAC cells.
  • To explore the underlying molecular mechanisms involving miR-125a-3p and its potential targets.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) to assess miR-125a-3p expression.
  • MTT assay and flow cytometry for cell viability and apoptosis.
  • Scratch wound healing and Transwell invasion assays to evaluate EMT.
  • Dual luciferase reporter assay to confirm direct targeting of Fyn by miR-125a-3p.
  • Western blot to analyze protein expression levels.

Main Results:

  • miR-125a-3p expression decreased in PDAC cells following gemcitabine treatment.
  • Overexpression of miR-125a-3p enhanced sensitivity to gemcitabine and suppressed EMT.
  • miR-125a-3p directly targets Fyn, reducing its expression and subsequent EMT promotion.
  • Fyn overexpression partially reversed the chemosensitizing effects of miR-125a-3p.

Conclusions:

  • miR-125a-3p plays a crucial role in chemosensitivity in PDAC.
  • miR-125a-3p inhibits EMT by directly targeting Fyn.
  • This finding presents a potential therapeutic strategy to overcome chemoresistance in PDAC.
Keywords:
ChemosensitivityEMTFynPDACmiR-125a-3p

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