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SP1-Mediated Upregulation of Long Noncoding RNA ZFAS1 Involved in Non-syndromic Cleft Lip and Palate via Inactivating WNT/β-Catenin Signaling Pathway

Non-syndromic cleft lip and palate (NSCLP) is one of the most common congenital malformations with multifactorial etiology. Although long non-coding RNAs (lncRNAs) have been implicated in the development of lip and palate, their roles in NSCLP are not fully elucidated. This study aimed to investigat...

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Autores principales: Chen, Shiyu, Jia, Zhonglin, Cai, Ming, Ye, Mujie, Wu, Dandan, Wan, Teng, Zhang, Bowen, Wu, Peixuan, Xu, Yuexin, Guo, Yuntao, Tian, Chan, Ma, Duan, Ma, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275830/
https://www.ncbi.nlm.nih.gov/pubmed/34268302
http://dx.doi.org/10.3389/fcell.2021.662780
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author Chen, Shiyu
Jia, Zhonglin
Cai, Ming
Ye, Mujie
Wu, Dandan
Wan, Teng
Zhang, Bowen
Wu, Peixuan
Xu, Yuexin
Guo, Yuntao
Tian, Chan
Ma, Duan
Ma, Jing
author_facet Chen, Shiyu
Jia, Zhonglin
Cai, Ming
Ye, Mujie
Wu, Dandan
Wan, Teng
Zhang, Bowen
Wu, Peixuan
Xu, Yuexin
Guo, Yuntao
Tian, Chan
Ma, Duan
Ma, Jing
author_sort Chen, Shiyu
collection PubMed
description Non-syndromic cleft lip and palate (NSCLP) is one of the most common congenital malformations with multifactorial etiology. Although long non-coding RNAs (lncRNAs) have been implicated in the development of lip and palate, their roles in NSCLP are not fully elucidated. This study aimed to investigate how dysregulated lncRNAs contribute to NSCLP. Using lncRNA sequencing, bioinformatics analysis, and clinical tissue sample detection, we identified that lncRNA ZFAS1 was significantly upregulated in NSCLP. The upregulation of ZFAS1 mediated by SP1 transcription factor (SP1) inhibited expression levels of Wnt family member 4 (WNT4) through the binding with CCCTC-binding factor (CTCF), subsequently inactivating the WNT/β-catenin signaling pathway, which has been reported to play a significant role on the development of lip and palate. Moreover, in vitro, the overexpression of ZFAS1 inhibited cell proliferation and migration in human oral keratinocytes and human umbilical cord mesenchymal stem cells (HUC-MSCs) and also repressed chondrogenic differentiation of HUC-MSCs. In vivo, ZFAS1 suppressed cell proliferation and numbers of chondrocyte in the zebrafish ethmoid plate. In summary, these results indicated that ZFAS1 may be involved in NSCLP by affecting cell proliferation, migration, and chondrogenic differentiation through inactivating the WNT/β-catenin signaling pathway.
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spelling pubmed-82758302021-07-14 SP1-Mediated Upregulation of Long Noncoding RNA ZFAS1 Involved in Non-syndromic Cleft Lip and Palate via Inactivating WNT/β-Catenin Signaling Pathway Chen, Shiyu Jia, Zhonglin Cai, Ming Ye, Mujie Wu, Dandan Wan, Teng Zhang, Bowen Wu, Peixuan Xu, Yuexin Guo, Yuntao Tian, Chan Ma, Duan Ma, Jing Front Cell Dev Biol Cell and Developmental Biology Non-syndromic cleft lip and palate (NSCLP) is one of the most common congenital malformations with multifactorial etiology. Although long non-coding RNAs (lncRNAs) have been implicated in the development of lip and palate, their roles in NSCLP are not fully elucidated. This study aimed to investigate how dysregulated lncRNAs contribute to NSCLP. Using lncRNA sequencing, bioinformatics analysis, and clinical tissue sample detection, we identified that lncRNA ZFAS1 was significantly upregulated in NSCLP. The upregulation of ZFAS1 mediated by SP1 transcription factor (SP1) inhibited expression levels of Wnt family member 4 (WNT4) through the binding with CCCTC-binding factor (CTCF), subsequently inactivating the WNT/β-catenin signaling pathway, which has been reported to play a significant role on the development of lip and palate. Moreover, in vitro, the overexpression of ZFAS1 inhibited cell proliferation and migration in human oral keratinocytes and human umbilical cord mesenchymal stem cells (HUC-MSCs) and also repressed chondrogenic differentiation of HUC-MSCs. In vivo, ZFAS1 suppressed cell proliferation and numbers of chondrocyte in the zebrafish ethmoid plate. In summary, these results indicated that ZFAS1 may be involved in NSCLP by affecting cell proliferation, migration, and chondrogenic differentiation through inactivating the WNT/β-catenin signaling pathway. Frontiers Media S.A. 2021-06-29 /pmc/articles/PMC8275830/ /pubmed/34268302 http://dx.doi.org/10.3389/fcell.2021.662780 Text en Copyright © 2021 Chen, Jia, Cai, Ye, Wu, Wan, Zhang, Wu, Xu, Guo, Tian, Ma and Ma. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Chen, Shiyu
Jia, Zhonglin
Cai, Ming
Ye, Mujie
Wu, Dandan
Wan, Teng
Zhang, Bowen
Wu, Peixuan
Xu, Yuexin
Guo, Yuntao
Tian, Chan
Ma, Duan
Ma, Jing
SP1-Mediated Upregulation of Long Noncoding RNA ZFAS1 Involved in Non-syndromic Cleft Lip and Palate via Inactivating WNT/β-Catenin Signaling Pathway
title SP1-Mediated Upregulation of Long Noncoding RNA ZFAS1 Involved in Non-syndromic Cleft Lip and Palate via Inactivating WNT/β-Catenin Signaling Pathway
title_full SP1-Mediated Upregulation of Long Noncoding RNA ZFAS1 Involved in Non-syndromic Cleft Lip and Palate via Inactivating WNT/β-Catenin Signaling Pathway
title_fullStr SP1-Mediated Upregulation of Long Noncoding RNA ZFAS1 Involved in Non-syndromic Cleft Lip and Palate via Inactivating WNT/β-Catenin Signaling Pathway
title_full_unstemmed SP1-Mediated Upregulation of Long Noncoding RNA ZFAS1 Involved in Non-syndromic Cleft Lip and Palate via Inactivating WNT/β-Catenin Signaling Pathway
title_short SP1-Mediated Upregulation of Long Noncoding RNA ZFAS1 Involved in Non-syndromic Cleft Lip and Palate via Inactivating WNT/β-Catenin Signaling Pathway
title_sort sp1-mediated upregulation of long noncoding rna zfas1 involved in non-syndromic cleft lip and palate via inactivating wnt/β-catenin signaling pathway
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275830/
https://www.ncbi.nlm.nih.gov/pubmed/34268302
http://dx.doi.org/10.3389/fcell.2021.662780
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