PMID- 34268302 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210717 IS - 2296-634X (Print) IS - 2296-634X (Electronic) IS - 2296-634X (Linking) VI - 9 DP - 2021 TI - SP1-Mediated Upregulation of Long Noncoding RNA ZFAS1 Involved in Non-syndromic Cleft Lip and Palate via Inactivating WNT/beta-Catenin Signaling Pathway. PG - 662780 LID - 10.3389/fcell.2021.662780 [doi] LID - 662780 AB - 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/beta-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/beta-catenin signaling pathway. CI - Copyright (c) 2021 Chen, Jia, Cai, Ye, Wu, Wan, Zhang, Wu, Xu, Guo, Tian, Ma and Ma. FAU - Chen, Shiyu AU - Chen S AD - Institutes of Biomedical Sciences, Fudan University, Shanghai, China. FAU - Jia, Zhonglin AU - Jia Z AD - State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases and Department of Cleft Lip and Palate, West China Hospital of Stomatology, Sichuan University, Chengdu, China. FAU - Cai, Ming AU - Cai M AD - Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Ye, Mujie AU - Ye M AD - Children's Hospital of Fudan University, Shanghai, China. FAU - Wu, Dandan AU - Wu D AD - Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Wan, Teng AU - Wan T AD - Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Zhang, Bowen AU - Zhang B AD - School of Basic Medical Sciences, Fudan University, Shanghai, China. FAU - Wu, Peixuan AU - Wu P AD - School of Basic Medical Sciences, Fudan University, Shanghai, China. FAU - Xu, Yuexin AU - Xu Y AD - School of Basic Medical Sciences, Fudan University, Shanghai, China. FAU - Guo, Yuntao AU - Guo Y AD - Medical Laboratory of Nantong ZhongKe, Nantong, China. FAU - Tian, Chan AU - Tian C AD - Center for Reproductive Medicine, Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Ministry of Education, Beijing, China. AD - Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Peking University Third Hospital, Beijing, China. AD - Key Laboratory of Assisted Reproduction, Peking University, Beijing, China. FAU - Ma, Duan AU - Ma D AD - Institutes of Biomedical Sciences, Fudan University, Shanghai, China. AD - School of Basic Medical Sciences, Fudan University, Shanghai, China. AD - Children's Hospital of Fudan University, Shanghai, China. FAU - Ma, Jing AU - Ma J AD - ENT Institute, Department of Facial Plastic and Reconstructive Surgery, Eye & ENT Hospital, Fudan University, Shanghai, China. LA - eng PT - Journal Article DEP - 20210629 PL - Switzerland TA - Front Cell Dev Biol JT - Frontiers in cell and developmental biology JID - 101630250 PMC - PMC8275830 OTO - NOTNLM OT - CTCF OT - NSCLP OT - Sp1 OT - Wnt/beta-catenin pathway OT - ZFAS1 COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/07/17 06:00 MHDA- 2021/07/17 06:01 PMCR- 2021/01/01 CRDT- 2021/07/16 06:41 PHST- 2021/02/01 00:00 [received] PHST- 2021/05/27 00:00 [accepted] PHST- 2021/07/16 06:41 [entrez] PHST- 2021/07/17 06:00 [pubmed] PHST- 2021/07/17 06:01 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fcell.2021.662780 [doi] PST - epublish SO - Front Cell Dev Biol. 2021 Jun 29;9:662780. doi: 10.3389/fcell.2021.662780. eCollection 2021.