A screen identifies the oncogenic micro-RNA miR-378a-5p as a negative regulator of oncogene-induced senescence

Susanne Marije Kooistra1, Lise Christine Rudkjær Nørgaard1, Michael James Lees1

  • 1Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark; Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark.

Plos One
|March 22, 2014
PubMed

Insights

MicroRNAs can influence cancer development. Researchers found that miR-378a-5p delays oncogene-induced senescence (OIS), a process that normally prevents tumor formation, suggesting a pro-tumor role for this microRNA.

Area of Science:

  • Cellular senescence
  • Oncogenesis
  • MicroRNA biology

Background:

  • Oncogene-induced senescence (OIS) acts as a tumor suppressor mechanism.
  • Identifying factors that regulate OIS is crucial for understanding cancer development.

Purpose of the Study:

  • To discover novel microRNAs that can modulate OIS.
  • To investigate the role of miR-378a-5p in OIS and its potential impact on tumorigenesis.

Main Methods:

  • Screening for microRNAs affecting OIS in human diploid fibroblasts.
  • Assessing senescence markers (e.g., p16INK4A, senescence-associated β-galactosidase) upon ectopic miR-378a-5p expression.
  • Analyzing miR-378a-5p targets to elucidate its mechanism of action.

Main Results:

  • miR-378a-5p was identified as a microRNA capable of inhibiting OIS.
  • Ectopic miR-378a-5p expression reduced senescence markers and maintained proliferative capacity in the presence of oncogenic BRAF.
  • Several miR-378a-5p targets were identified, providing mechanistic insights into OIS delay.

Conclusions:

  • miR-378a-5p delays oncogene-induced senescence in human diploid fibroblasts.
  • This delay in OIS by miR-378a-5p may contribute to tumor formation, aligning with its known pro-oncogenic function.

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