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Updated: May 2, 2026

Genome-wide Screen for miRNA Targets Using the MISSION Target ID Library
Published on: April 6, 2012
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.
Abstract:
Oncogene-induced senescence (OIS) can occur in response to hyperactive oncogenic signals and is believed to be a fail-safe mechanism protecting against tumorigenesis. To identify new factors involved in OIS, we performed a screen for microRNAs that can overcome or inhibit OIS in human diploid fibroblasts. This screen led to the identification of miR-378a-5p and in addition several other miRNAs that have previously been shown to play a role in senescence. We show that ectopic expression of miR-378a-5p reduces the expression of several senescence markers, including p16(INK4A) and senescence-associated β-galactosidase. Moreover, cells with ectopic expression of miR-378a-5p retain proliferative capacity even in the presence of an activated Braf oncogene. Finally, we identified several miR-378a-5p targets in diploid fibroblasts that might explain the mechanism by which the microRNA can delay OIS. We speculate that miR-378a-5p might positively influence tumor formation by delaying OIS, which is consistent with a known pro-oncogenic function of this microRNA.
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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