MicroRNA-34c acts as a bidirectional switch in the maturation of insulin-producing cells derived from mesenchymal stem cells

Oncotarget
Chunyu BaiWeijun Guan

Abstract

miRNAs regulate insulin secretion, pancreatic development, and beta-cell differentiation. However, their function in the differentiation of IPCs from MSCs is poorly understood. In this study, to screen for miRNAs and their targets that function during the formation of IPCs from MSCs, we examined the miRNA expression profiles of MSCs and IPCs using RNA-seq and qPCR to confirm the above results. We found that miR-34c exhibited transient upregulation at an early stage of the formation of IPCs derived from MSCs. Next, we analyzed the biological function of miR-34c by predicting its targets using bioinformatic tools. Combining our data with those from previous reports, we found that miR-34c and its targets play an important role in the formation of IPCs. Therefore, we overexpressed miR-34c and expressed small interfering RNAs of its targets in MSCs to investigate their functions in IPC formation. We found that miR-34c acts as a bidirectional switch in the formation of IPCs derived from MSCs by regulating the expression of targets to affect insulin synthesis and secretion. miR-34c was shown to downregulate its targets, including PDE7B, PDGFRA, and MAP2K1, to increase proinsulin synthesis, but when miR-34c continually dysregulated suc...Continue Reading

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Citations

Dec 31, 2019·Current Drug Targets·Adele SoltaniAbdolamir Allameh
Jan 11, 2020·Frontiers in Cell and Developmental Biology·Yuhua GaoChunyu Bai
Jan 30, 2021·Frontiers in Cell and Developmental Biology·Brittany J BisnettMichael Boyce
May 25, 2021·Journal of Agricultural and Food Chemistry·Xin WangJian Liu

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Methods Mentioned

BETA
RNA-seq
flow cytometry
PCR
GTPase
transfection
ELISA
reverse-transcription PCR
transfections
confocal microscopy

Software Mentioned

CXP
R package
miRDB
Venn Tools
DEGseq
Illumina Genome Analyzer Pipeline
Venny
TargetScan
miRbase

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