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MiR-22-3p Inhibits 5-Fluorouracil Resistance in Cholangiocarcinoma Cells Through PTEN/PI3K/AKT Axis

Ningrong Zhang1, Li Zang1

  • 1Department of Pharmacy, Ningbo Haishu People's Hospital, Ningbo, Republic of China.

Assay and Drug Development Technologies
|July 5, 2024
PubMed

Insights

MicroRNA-22-3p (miR-22-3p) suppresses cholangiocarcinoma (CCA) progression and enhances 5-fluorouracil (5-Fu) sensitivity. Overexpressing miR-22-3p inhibits the PTEN/PI3K/AKT pathway, promoting apoptosis in 5-Fu-resistant CCA cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Cholangiocarcinoma (CCA) is a globally prevalent and lethal cancer.
  • MicroRNAs (miRNAs) are implicated in CCA progression, but their role in 5-fluorouracil (5-Fu) resistance is unclear.

Purpose of the Study:

  • To investigate the impact of miR-22-3p on CCA resistance to 5-Fu.
  • To elucidate the underlying molecular mechanisms involving the PTEN/PI3K/AKT pathway.

Main Methods:

  • Bioinformatics analysis to correlate miR-22-3p with CCA progression, diagnosis, and survival.
  • Validation of miR-22-3p expression in CCA cell lines.
  • Functional assays to assess the effect of miR-22-3p on 5-Fu-resistant CCA cells and PTEN expression.
  • Verification of the miR-22-3p/PTEN/PI3K/AKT regulatory network.

Main Results:

  • miR-22-3p was significantly downregulated in CCA cell lines.
  • Elevated miR-22-3p inhibited proliferation and activity of 5-Fu-resistant CCA cells.
  • PTEN was identified as a direct target of miR-22-3p, with its expression correlating with patient survival.
  • Reduced PTEN expression promoted apoptosis in 5-Fu-resistant CCA cells.
  • The miR-22-3p/PTEN/PI3K/AKT axis was confirmed to influence 5-Fu sensitivity in CCA.

Conclusions:

  • miR-22-3p functions as a tumor suppressor in CCA.
  • Overexpression of miR-22-3p inhibits the PTEN/PI3K/AKT pathway, enhancing apoptosis and increasing CCA sensitivity to 5-Fu.
  • miR-22-3p represents a potential therapeutic target for overcoming 5-Fu resistance in cholangiocarcinoma.
Keywords:
5-Fluorouracil resistancePTEN/PI3K/AKT axiscell apoptosischolangiocarcinomamiR-22-3p

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