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Updated: May 26, 2026

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
08:40

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library

Published on: April 6, 2012

MicroRNA-128-2 targets the transcriptional repressor E2F5 enhancing mutant p53 gain of function

S Donzelli1, G Fontemaggi, F Fazi

  • 1Translational Oncogenomics Unit, National Cancer Institute Regina Elena Rome, Italy.

Cell Death and Differentiation
|December 24, 2011
PubMed

Insights

Mutant p53 in non-small-cell lung cancer (NSCLC) drives chemoresistance by inducing microRNA-128-2. This microRNA inhibits apoptosis and enhances resistance to common chemotherapy drugs.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • p53 mutations are critical in non-small-cell lung cancer (NSCLC) development and treatment resistance.
  • Mutant p53 proteins often exhibit oncogenic functions and are highly expressed in tumors.

Purpose of the Study:

  • To investigate the role of the p53R175H mutant in regulating microRNA expression in NSCLC.
  • To elucidate the mechanism by which mutant p53-induced microRNAs contribute to chemoresistance in NSCLC.

Main Methods:

  • Analysis of p53R175H binding to the ARPP21 promoter.
  • Measurement of ARPP21 mRNA and miR-128-2 expression levels.
  • Assessment of apoptosis and chemoresistance in lung cancer cells with altered miR-128-2 expression.
  • Identification of miR-128-2 targets and downstream effects on apoptosis pathways.

Main Results:

  • The p53R175H mutant induces the expression of miR-128-2 by binding to the ARPP21 promoter.
  • Increased miR-128-2 expression in lung cancer cells leads to reduced apoptosis and enhanced resistance to cisplatin, doxorubicin, and 5-fluorouracil.
  • miR-128-2 post-transcriptionally targets E2F5, abrogating its repression of p21(waf1) transcription.
  • Cytoplasmic p21(waf1) protein prevents pro-caspase-3 cleavage, contributing to an anti-apoptotic effect.

Conclusions:

  • miR-128-2 acts as a key regulator in conferring chemoresistance in non-small-cell lung cancer.
  • The p53-miR-128-2 axis represents a potential therapeutic target for overcoming NSCLC chemoresistance.

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