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Effects of miRNA‐342‐3p in modulating Hedgehog signaling pathway of human umbilical cord mesenchymal stem cells by down‐regulating Sufu
Author(s) -
Qing Ying,
Huang Mengqi,
Cao Yingguang,
Du Tianfeng,
Song Ke
Publication year - 2019
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/odi.13068
Subject(s) - microrna , hedgehog signaling pathway , gene knockdown , mesenchymal stem cell , microbiology and biotechnology , biology , signal transduction , hedgehog , sonic hedgehog , transforming growth factor , cancer research , gene , genetics
Objective Previously, we have shown that miRNA‐342‐3p was increased during osteogenic differentiation of human umbilical mesenchymal stem cells (hUCMSCs) via regulating the sonic hedgehog (Shh) pathway. In this study, our objective is to further investigate the role of miRNA‐342‐3p in activation of Shh pathway by targeting suppressor of fused protein (Sufu), a suppressor of transcriptional factor Gli, as well as the potential interaction with transforming growth factor beta (TGF‐β) signaling pathway during osteogenic induction of hUCMSCs. Materials and methods HUCMSCs that stable overexpression or knockdown of miRNA‐342‐3p were established by infection with lentiviral vectors. mRNA and protein levels of Hedgehog signaling pathway and osteogenic genes were measured by RT‐qPCR and western blot assays. Luciferase reporter assay was performed to test the direct binding site of Sufu 5′UTR targeted by miRNA‐342‐3p. Results Overexpression of miRNA‐342‐3p in hUCMSCs enhanced the expression of osteogenic genes by targeting Sufu. And the potential of osteogenic differentiation of hUCMSCs was inhibited while knocking down miRNA‐342‐3p. Meanwhile, induced the TGF‐β expression level was also observed upon overexpressing miRNA‐342‐3p, suggesting activation of TGF‐β signaling pathway was a potential mechanism of miRNA‐342‐3p‐mediated osteogenesis in hUCMSCs. Conclusions Our findings provide new mechanistic evidence that miRNA‐342‐3p might be a valuable therapeutic target in bone regeneration.