PMID- 33546582
OWN - NLM
STAT- MEDLINE
DCOM- 20211001
LR  - 20211001
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Print)
IS  - 1076-1551 (Linking)
VI  - 27
IP  - 1
DP  - 2021 Feb 5
TI  - Long non-coding RNA CIR inhibits chondrogenic differentiation of mesenchymal stem 
      cells by epigenetically suppressing ATOH8 via methyltransferase EZH2.
PG  - 12
LID - 10.1186/s10020-021-00272-9 [doi]
LID - 12
AB  - BACKGROUND: Osteoarthritis (OA) is the most common articular disorder, leading to 
      joint malfunction and disability. Although the incidence of OA is increasing 
      globally, the treatment of OA is very limited. LncRNA CIR has been implicated in 
      OA through unclear mechanisms. Here, we investigated the role of lncRNA CIR in 
      chondrogenic differentiation. METHODS: Human umbilical-cord-derived mesenchymal 
      stem cells (hUC-MSCs) were obtained from human umbilical cords. Flow cytometry 
      was used to analyze the surface markers of hUC-MSCs. Various culture conditions 
      and corresponding staining assays were employed to assess the differentiation 
      abilities of hUC-MSC. qRT-PCR, western blot, and immunostaining were used to 
      measure expression levels of related genes and proteins such as lncRNA CIR, 
      ATOH8, EZH2, and H3K27me3. RNA immunoprecipitation assay, biotin pull-down, and 
      chromatin immunoprecipitaion assay were performed to analyze the interactions of 
      lncRNA CIR, EZH2, H3K27me3 and ATOH8 promoter. RESULTS: hUC-MSCs exhibited MSCs 
      features and could differentiate into chondrocytes under specific conditions. 
      LncRNA CIR was downregulated while ATOH8 was upregulated during the chondrogenic 
      differentiation of hUC-MSCs. Knockdown lncRNA CIR or overexpression of ATOH8 
      promoted chondrogenic differentiation. Further, lncRNA CIR bound to EZH2 and 
      repressed ATOH8 expression via EZH2-mediated H3K27me3, which promotes the 
      methylation of ATOH8. Inhibition of ATOH8 reversed the effects of knockdown 
      lncRNA CIR on chondrogenic differentiation. CONCLUSION: LncRNA CIR suppresses 
      chondrogenic differentiation of hUC-MSCs. Mechanistically, lncRNA CIR could 
      inhibit ATOH8 expression that functions to promote chondrogenic differentiation 
      through EZH2-mediated epigenetic modifications.
FAU - Liu, Feng
AU  - Liu F
AD  - Department of Orthopedics, The Second Xiangya Hospital of Central South 
      University, No.139 Renminzhong Road, Changsha, 410011, Hunan, People's Republic 
      of China.
AD  - Department of Orthopedics, The Third Hospital of Changsha, Changsha, 410015, 
      Hunan, People's Republic of China.
FAU - Song, De-Ye
AU  - Song DY
AD  - Department of Orthopedics, The Second Xiangya Hospital of Central South 
      University, No.139 Renminzhong Road, Changsha, 410011, Hunan, People's Republic 
      of China.
FAU - Huang, Jun
AU  - Huang J
AD  - Department of Orthopedics, The Second Xiangya Hospital of Central South 
      University, No.139 Renminzhong Road, Changsha, 410011, Hunan, People's Republic 
      of China.
FAU - Yang, Hong-Qi
AU  - Yang HQ
AD  - Department of Orthopedics, The Third Hospital of Changsha, Changsha, 410015, 
      Hunan, People's Republic of China.
FAU - You, Di
AU  - You D
AD  - Department of Orthopedics, The Second Xiangya Hospital of Central South 
      University, No.139 Renminzhong Road, Changsha, 410011, Hunan, People's Republic 
      of China.
FAU - Ni, Jiang-Dong
AU  - Ni JD
AUID- ORCID: 0000-0001-5245-722X
AD  - Department of Orthopedics, The Second Xiangya Hospital of Central South 
      University, No.139 Renminzhong Road, Changsha, 410011, Hunan, People's Republic 
      of China. nijiangdong@csu.deu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210205
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0 (ATOH8 protein, human)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Histones)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (long noncoding RNA CIR, human)
RN  - EC 2.1.1.43 (EZH2 protein, human)
RN  - EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein)
SB  - IM
MH  - Adult
MH  - Basic Helix-Loop-Helix Transcription Factors/*genetics
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Chondrocytes/*cytology/metabolism
MH  - Chondrogenesis
MH  - DNA Methylation
MH  - Enhancer of Zeste Homolog 2 Protein/*genetics
MH  - Epigenesis, Genetic
MH  - Female
MH  - Histones
MH  - Humans
MH  - Mesenchymal Stem Cells/*cytology/metabolism
MH  - Pregnancy
MH  - Promoter Regions, Genetic
MH  - RNA, Long Noncoding/*genetics
PMC - PMC7866678
OTO - NOTNLM
OT  - ATOH8
OT  - Chondrogenic differentiation
OT  - EZH2
OT  - LncRNA CIR
OT  - Osteoarthritis
OT  - hUC-MSC
COIS- The authors declare that they have no competing interests.
EDAT- 2021/02/07 06:00
MHDA- 2021/10/02 06:00
PMCR- 2021/02/05
CRDT- 2021/02/06 05:26
PHST- 2020/09/09 00:00 [received]
PHST- 2021/01/13 00:00 [accepted]
PHST- 2021/02/06 05:26 [entrez]
PHST- 2021/02/07 06:00 [pubmed]
PHST- 2021/10/02 06:00 [medline]
PHST- 2021/02/05 00:00 [pmc-release]
AID - 10.1186/s10020-021-00272-9 [pii]
AID - 272 [pii]
AID - 10.1186/s10020-021-00272-9 [doi]
PST - epublish
SO  - Mol Med. 2021 Feb 5;27(1):12. doi: 10.1186/s10020-021-00272-9.