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Published on: May 21, 2019
The miR-30 family microRNAs confer epithelial phenotype to human pancreatic cells
Mugdha V Joglekar1, Deepak Patil, Vinay M Joglekar
1Stem Cells and Diabetes Section, National Center for Cell Science, Ganeshkhind Road, Pune, India.
Abstract:
Epithelial-to-mesenchymal transition is a phenomenon necessary for embryonic development and also seen during certain pathological conditions. We show here for the first time that reduction in miR-30 family microRNAs, is responsible for mesenchymal transition of primary cultures of human pancreatic epithelial cells. We found that miR-30 family microRNAs target mesenchymal gene transcripts and maintain them in a translationally inactive state. Forced depletion using miR-30 family specific anti-miRs leads to mesenchymal transition while ectopic overexpression maintains the epithelial phenotype. We also show that miR-30 family microRNAs increase in abundance during differentiation of pancreatic islet-derived mesenchymal cells into hormone-producing islet-like cell aggregates. Our studies in human adult diseased pancreas also demonstrate that miR-30 family microRNAs are expressed at lower abundance in fibrotic lesions during pancreatitis. Together, our data confirm that miR-30 family microRNAs form a part of the regulatory signaling events involved in cellular response of pancreatic epithelial cells during mesenchymal transition.
Insights
Reduced miR-30 family microRNAs drive mesenchymal transition in human pancreatic cells. These microRNAs normally suppress this transition, crucial in development and disease.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- Epithelial-to-mesenchymal transition (EMT) is vital for embryonic development.
- EMT is also implicated in pathological conditions, including fibrosis.
- The specific role of microRNAs in pancreatic EMT is not fully understood.
Purpose of the Study:
- To investigate the role of miR-30 family microRNAs in human pancreatic epithelial cells.
- To determine if miR-30 family microRNAs regulate EMT in pancreatic cells.
- To explore the therapeutic potential of modulating miR-30 levels in pancreatic diseases.
Main Methods:
- Primary culture of human pancreatic epithelial cells.
- Manipulation of miR-30 family microRNA levels using anti-miRs and overexpression vectors.
- Analysis of mesenchymal gene expression and protein translation.
- Study of miR-30 expression in differentiating pancreatic cells and diseased pancreas.
Main Results:
- Reduction in miR-30 family microRNAs induces mesenchymal transition in human pancreatic epithelial cells.
- miR-30 family microRNAs target and translationally repress mesenchymal gene transcripts.
- Depletion of miR-30 promotes EMT, while overexpression maintains the epithelial phenotype.
- miR-30 family microRNAs are upregulated during pancreatic islet cell differentiation and downregulated in fibrotic pancreatitis lesions.
Conclusions:
- miR-30 family microRNAs are key regulators of EMT in human pancreatic epithelial cells.
- These microRNAs act as suppressors of the mesenchymal phenotype.
- Dysregulation of miR-30 family microRNAs may contribute to pancreatic fibrosis and disease.
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