PMID- 30790389 OWN - NLM STAT- MEDLINE DCOM- 20191230 LR - 20191230 IS - 1601-0825 (Electronic) IS - 1354-523X (Linking) VI - 25 IP - 4 DP - 2019 May TI - Effects of miRNA-342-3p in modulating Hedgehog signaling pathway of human umbilical cord mesenchymal stem cells by down-regulating Sufu. PG - 1147-1157 LID - 10.1111/odi.13068 [doi] AB - 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-beta) 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-beta expression level was also observed upon overexpressing miRNA-342-3p, suggesting activation of TGF-beta 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. CI - (c) 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved. FAU - Qing, Ying AU - Qing Y AUID- ORCID: 0000-0002-9551-8907 AD - Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Huang, Mengqi AU - Huang M AD - Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Cao, Yingguang AU - Cao Y AD - Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Du, Tianfeng AU - Du T AD - Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. FAU - Song, Ke AU - Song K AD - Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. LA - eng GR - 81400490/National Natural Science Foundation of China/ PT - Journal Article DEP - 20190311 PL - Denmark TA - Oral Dis JT - Oral diseases JID - 9508565 RN - 0 (Hedgehog Proteins) RN - 0 (MIRN342 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Repressor Proteins) RN - 0 (SUFU protein, human) MH - Bone Regeneration MH - Cell Differentiation MH - *Hedgehog Proteins MH - Humans MH - *Mesenchymal Stem Cells MH - *MicroRNAs MH - *Osteogenesis MH - *Repressor Proteins MH - Signal Transduction MH - *Umbilical Cord OTO - NOTNLM OT - Hedgehog signaling pathway OT - Sufu OT - hUCMSCs OT - miRNA-342-3p OT - osteogenesis EDAT- 2019/02/23 06:00 MHDA- 2019/12/31 06:00 CRDT- 2019/02/22 06:00 PHST- 2018/10/19 00:00 [received] PHST- 2019/02/03 00:00 [revised] PHST- 2019/02/15 00:00 [accepted] PHST- 2019/02/23 06:00 [pubmed] PHST- 2019/12/31 06:00 [medline] PHST- 2019/02/22 06:00 [entrez] AID - 10.1111/odi.13068 [doi] PST - ppublish SO - Oral Dis. 2019 May;25(4):1147-1157. doi: 10.1111/odi.13068. Epub 2019 Mar 11.