MiR-31 regulates the cisplatin resistance by targeting Src in gallbladder cancer

Maolan Li1,2, Wei Chen1, Hongchen Zhang1,2

  • 1Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.

Oncotarget
|November 9, 2016
PubMed
Abstract

Insights

MicroRNA-31 (miR-31) is significantly reduced in gallbladder cancer (GBC) cells, contributing to cisplatin resistance. Upregulating miR-31 enhances chemosensitivity, offering a potential therapeutic strategy for GBC drug resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Gallbladder cancer (GBC) exhibits high resistance to chemotherapy.
  • MicroRNAs (miRNAs) play a crucial role in cancer development and chemoresistance.
  • Understanding miRNA regulation is key to overcoming drug resistance in GBC.

Purpose of the Study:

  • To investigate the role of specific microRNAs in regulating cisplatin (DDP) susceptibility in GBC.
  • To identify the underlying molecular pathways involved in miRNA-mediated chemoresistance.
  • To explore the therapeutic potential of targeting miRNAs to overcome DDP resistance in GBC.

Main Methods:

  • Microarray analysis to identify differentially expressed miRNAs in DDP-resistant GBC cells.
  • In vitro assays (wound healing, transwell, CCK-8, colony formation, flow cytometry) to assess cell behavior.
  • Xenograft tumor models to validate the in vivo function of the target miRNA and its downstream pathways.

Main Results:

  • MicroRNA-31 (miR-31) showed the most significant fold change in DDP-resistant GBC cells.
  • Overexpression of miR-31 reduced GBC cell proliferation, viability, and invasion while promoting apoptosis.
  • Knockdown of Src proto-oncogene (Src) expression increased apoptosis and DDP-chemosensitivity, effects reversed by Src rescue.

Conclusions:

  • miR-31 expression is significantly reduced in cisplatin-resistant GBC cells.
  • Upregulating miR-31 enhances chemosensitivity and overcomes DDP resistance in GBC.
  • miR-31 presents a promising therapeutic target for improving GBC treatment outcomes.