Journal
ONCOTARGET
Volume 7, Issue 39, Pages 63561-63570Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.11538
Keywords
mesenchymal stem cells; HoxA-AS3; lineage specification; enhancer of zeste homolog 2; long non-coding RNA
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Funding
- National Natural Science Foundation of China [81500354, 81500667]
- Natural Science Foundation of China [81502458]
- Shenzhen Science Foundation [JCYJ20140828163633987, JCYJ20160308104109234]
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Long non-coding RNAs (lncRNAs) play an important role in gene regulation and are involving in diverse cellular processes. However, their roles in reprogramming of gene expression profiles during lineage commitment and maturation of mesenchymal stem cells (MSCs) remain poorly understood. In the current study, we characterize the expression of a lncRNA, HoxA-AS3, during the differentiation of MSCs. We showed that HoxA-AS3 is increased upon adipogenic induction of MSCs, while HoxA-AS3 remains unaltered during osteogenic induction. Silencing of HoxA-AS3 in MSCs resulted in decreased adipogenesis and expression of adipogenic markerws, PPARG, CEBPA, FABP4 and ADIPOQ. Conversely, knockdown of HoxA-AS3 expression in MSCs exhibited an enhanced osteogenesis and osteogenic markers expression, including RUNX2, SP7, COL1A1, IBSP, BGLAP and SPP1. Mechanistically, HoxA-AS3 interacts with Enhancer Of Zeste 2 (EZH2) and is required for H3 lysine-27 trimethylation (H3K27me3) of key osteogenic transcription factor Runx2. Our data reveal that HoxA-AS3 acts as an epigenetic switch that determines the lineage specification of MSC.
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