miR302 regulates SNAI1 expression to control mesangial cell plasticity
L De Chiara1,2,3, D Andrews1,2, A Watson2
1UCD Diabetes Complications Research Centre, Conway Institute of Biomolecular and Biomedical Science, Dublin, Ireland.
Scientific Reports
|February 15, 2017
Summary
MicroRNA 302 (miR302) overexpression enhances cell plasticity by regulating epigenetic modifiers like EZH2 and transcription factors such as Snail. This offers potential for cell reprogramming and restoring regenerative states in adult cells.
Area of Science:
- Molecular Biology
- Epigenetics
- Cell Biology
Background:
- Cell fate is determined by transcription factors and epigenetic modifiers.
- Cell plasticity allows cells to change their identity and function.
- MicroRNAs (miRNAs) are key regulators of gene expression and cellular processes.
Purpose of the Study:
- To investigate the role of miR302 in regulating cell plasticity.
- To identify the molecular mechanisms underlying miR302-mediated cell plasticity.
- To explore the potential of miR302 for cell reprogramming.
Main Methods:
- Overexpression of miR302 in mesangial cells.
- Silencing of specific genes using esiRNA.
- Analysis of gene and protein expression (e.g., TGFβ type II receptor, Snail, EZH2, ZO-1, E-cadherin).
Main Results:
- miR302 overexpression silenced the TGFβ type II receptor, increasing cell plasticity.
- miR302 increased Snail and EZH2 expression, with Smad3 and EZH2 forming a regulatory complex.
- miR302 independently regulated EZH2 and Snail.
- Reprogramming was evidenced by de novo expression of tight junction proteins (ZO-1, E-cadherin).
Conclusions:
- miR302 plays a crucial role in regulating cell plasticity through epigenetic and transcriptional mechanisms.
- Targeting miR302 offers a potential therapeutic strategy for cell reprogramming and regeneration.
- Understanding epigenetic silencing in adult cells is key to addressing acquired diseases and restoring regenerative potential.
