Long noncoding RNA DANCR regulates miR-1305-Smad 4 axis to promote chondrogenic differentiation of human synovium-derived mesenchymal stem cells
Author(s) -
Lei Zhang,
Xiangyi Sun,
Shuo Chen,
Chao Yang,
Ben Shi,
Liwu Zhou,
Jianning Zhao
Publication year - 2017
Publication title -
bioscience reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.938
H-Index - 77
eISSN - 1573-4935
pISSN - 0144-8463
DOI - 10.1042/bsr20170347
Subject(s) - chondrogenesis , microrna , microbiology and biotechnology , mesenchymal stem cell , biology , long non coding rna , cellular differentiation , stem cell , smad , rna , cell growth , signal transduction , gene , genetics
miRNAs have been reported to regulate cellular differentiation by modulating multiple signaling pathways. Long noncoding RNA (lnc RNA) DANCR was previously identified to be critical for the chondrogenesis of human synovium-derived mesenchymal stem cells (SMSC), however, the underlying molecular mechanism requires better understanding. Here, miRNA expression profiling in DANCR overexpressed in SMSCs identified significant down-regulation of miR-1305 , which serves as a downstream target of DANCR. Notably, miR-1305 overexpression reversed DANCR-induced cell proliferation and chondrogenic differentiation of SMSCs, which suggested that miR-1305 antagonized the function of DANCR. Mechanistically, highly expressed miR-1305 resulted in the decreased expression of the TGF-β pathway member Smad4, and inhibition of miR-1305 enhanced the expression level of Smad4. Depletion of Smad4 suppressed the promotion of DANCR in cell proliferation and chondrogenesis of SMSCs. Collectively, our results characterized miR-1305 -Smad4 axis as a major downstream functional mechanism of lncRNA DANCR in promoting the chondrogenesis in SMSCs.
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