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2016 ; 7
(39
): 63561-63570
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Long non-coding RNA HoxA-AS3 interacts with EZH2 to regulate lineage commitment
of mesenchymal stem cells
#MMPMID27566578
Zhu XX
; Yan YW
; Chen D
; Ai CZ
; Lu X
; Xu SS
; Jiang S
; Zhong GS
; Chen DB
; Jiang YZ
Oncotarget
2016[Sep]; 7
(39
): 63561-63570
PMID27566578
show ga
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 markers,
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.
|Adipogenesis/*genetics
[MESH]
|Animals
[MESH]
|Cell Differentiation
[MESH]
|Cell Lineage/*genetics
[MESH]
|Cell Proliferation
[MESH]
|Cells, Cultured
[MESH]
|Enhancer of Zeste Homolog 2 Protein/genetics/*metabolism
[MESH]