title: Long non-coding RNA HoxA-AS3 interacts with EZH2 to regulate lineage commitment of mesenchymal stem cells.
abstract: 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.
authors: Institute for Advanced Study, Shenzhen University, Shenzhen, Guangdong, China.
authors: Xin-Xing
authors: XX
authors: Zhu
authors: Institute for Advanced Study, Shenzhen University, Shenzhen, Guangdong, China.
authors: Ya-Wei
authors: YW
authors: Yan
authors: School of Dentistry, University of California, Los Angeles, CA, USA.
authors: Demeng
authors: D
authors: Chen
authors: Institute for Advanced Study, Shenzhen University, Shenzhen, Guangdong, China.
authors: Chun-Zhi
authors: CZ
authors: Ai
authors: Department of Physiology, Center for Diabetes, Obesity and Metabolism, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, Guangdong, China.
authors: Xifeng
authors: X
authors: Lu
authors: Institute for Advanced Study, Shenzhen University, Shenzhen, Guangdong, China.
authors: Shan-Shan
authors: SS
authors: Xu
authors: Institute for Advanced Study, Shenzhen University, Shenzhen, Guangdong, China.
authors: Shan
authors: S
authors: Jiang
authors: Henan Key Laboratory of Neural Regeneration and Repairment, The First affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China.
authors: Gen-Shen
authors: GS
authors: Zhong
authors: Department of Obstetrics and Gynecology, University of California, Irvine, CA, USA.
authors: Dong-Bao
authors: DB
authors: Chen
authors: Institute for Advanced Study, Shenzhen University, Shenzhen, Guangdong, China.
authors: Yi-Zhou
authors: YZ
authors: Jiang
mesh_terms: D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics*; D049109:Cell Proliferation; D002478:Cells, Cultured; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*
chemical_list: D062085:RNA, Long Noncoding; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein
keywords: HoxA-AS3; enhancer of zeste homolog 2; lineage specification; long non-coding RNA; mesenchymal stem cells