PMID- 33493612
OWN - NLM
STAT- MEDLINE
DCOM- 20210319
LR  - 20210319
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 341
DP  - 2021 May 1
TI  - LncRNA Meg3-mediated regulation of the Smad pathway in atRA-induced cleft palate.
PG  - 51-58
LID - S0378-4274(21)00026-6 [pii]
LID - 10.1016/j.toxlet.2021.01.017 [doi]
AB  - Palatal mesenchymal cell proliferation is essential to the process of 
      palatogenesis, and the proliferation of mouse embryonic palate mesenchymal (MEPM) 
      cells is impacted by both all-trans retinoic acid (atRA) and the TGF-beta/Smad 
      signaling pathway. The long non-coding RNA (lncRNA) MEG3 has been shown to 
      activate TGF-beta/Smad signaling and to thereby regulate cell proliferation, 
      differentiation, and related processes. Herein, we found that atRA treatment (100 
      mg/kg) promoted Meg3 upregulation in MEPM cells, and that such upregulation was 
      linked to the suppression of MEPM cell proliferation in the context of secondary 
      palate fusion on gestational day (GD) 13 and 14. Moreover, the demethylation of 
      specific CpG sites within the lncRNA Meg3 promoter was detected in atRA-treated 
      MEPM cells, likely explaining the observed upregulation of this lncRNA. Smad 
      signaling was also suppressed by atRA treatment in these cells, and RNA 
      immunoprecipitation analyses revealed that Smad2 can directly interact with Meg3 
      in MEPM cells following atRA treatment. Therefore, we propose a model wherein 
      Meg3 is involved in the suppression of MEPM cell proliferation, functioning at 
      least in part via interacting with the Smad2 protein and thereby suppressing Smad 
      signaling in the context of atRA-induced cleft palate.
CI  - Copyright (c) 2021. Published by Elsevier B.V.
FAU - Liu, Xiaozhuan
AU  - Liu X
AD  - Center for Clinical Single-Cell Biomedicine, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
FAU - Zhang, Yuwei
AU  - Zhang Y
AD  - Center for Clinical Single-Cell Biomedicine, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
FAU - Shen, Lijun
AU  - Shen L
AD  - Center for Clinical Single-Cell Biomedicine, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
FAU - He, Zhidong
AU  - He Z
AD  - School of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
FAU - Chen, Yao
AU  - Chen Y
AD  - School of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
FAU - Li, Ning
AU  - Li N
AD  - College of Food Science and Technology, Henan Agricultural University, Zhengzhou, 
      Henan, China.
FAU - Zhang, Xiuli
AU  - Zhang X
AD  - Division of Blood Vessel Surgery, the First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou, Henan, China.
FAU - Zhang, Tingting
AU  - Zhang T
AD  - Center for Clinical Single-Cell Biomedicine, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
FAU - Gao, Suhua
AU  - Gao S
AD  - Center for Clinical Single-Cell Biomedicine, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
FAU - Yue, Haodi
AU  - Yue H
AD  - Center for Clinical Single-Cell Biomedicine, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
FAU - Li, Zhitao
AU  - Li Z
AD  - Medical College of Henan University of Science and Technology, Luoyang, Henan, 
      China.
FAU - Yu, Zengli
AU  - Yu Z
AD  - Center for Clinical Single-Cell Biomedicine, Henan Provincial People's Hospital, 
      People's Hospital of Zhengzhou University, Zhengzhou, Henan, China; School of 
      Public Health, Zhengzhou University, Zhengzhou, Henan, China. Electronic address: 
      zly@zzu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20210122
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Keratolytic Agents)
RN  - 0 (MEG3 non-coding RNA, human)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (Smad Proteins)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Animals
MH  - Cleft Palate/*chemically induced/metabolism
MH  - Female
MH  - Gene Expression Regulation, Developmental/drug effects
MH  - Keratolytic Agents/toxicity
MH  - Mice
MH  - Palate/drug effects/embryology/pathology
MH  - Pregnancy
MH  - RNA, Long Noncoding/genetics/*metabolism
MH  - Smad Proteins/genetics/*metabolism
MH  - Tretinoin/*adverse effects
OTO - NOTNLM
OT  - Cleft palate
OT  - MEPM
OT  - Meg3
OT  - TGF-beta/Smad signaling pathway
OT  - atRA
COIS- Declaration of Competing Interest The authors declare no conflict of interest.
EDAT- 2021/01/26 06:00
MHDA- 2021/03/20 06:00
CRDT- 2021/01/25 20:11
PHST- 2020/11/02 00:00 [received]
PHST- 2021/01/05 00:00 [revised]
PHST- 2021/01/18 00:00 [accepted]
PHST- 2021/01/26 06:00 [pubmed]
PHST- 2021/03/20 06:00 [medline]
PHST- 2021/01/25 20:11 [entrez]
AID - S0378-4274(21)00026-6 [pii]
AID - 10.1016/j.toxlet.2021.01.017 [doi]
PST - ppublish
SO  - Toxicol Lett. 2021 May 1;341:51-58. doi: 10.1016/j.toxlet.2021.01.017. Epub 2021 
      Jan 22.