PMID- 31044535 OWN - NLM STAT- MEDLINE DCOM- 20200806 LR - 20210109 IS - 1582-4934 (Electronic) IS - 1582-1838 (Print) IS - 1582-1838 (Linking) VI - 23 IP - 7 DP - 2019 Jul TI - LncRNA-SULT1C2A regulates Foxo4 in congenital scoliosis by targeting rno-miR-466c-5p through PI3K-ATK signalling. PG - 4582-4591 LID - 10.1111/jcmm.14355 [doi] AB - Congenital scoliosis (CS) is the result of anomalous vertebrae development, but the pathogenesis of CS remains unclear. Long non-coding RNAs (lncRNAs) have been implicated in embryo development, but their role in CS remains unknown. In this study, we investigated the role and mechanisms of a specific lncRNA, SULT1C2A, in somitogenesis in a rat model of vitamin A deficiency (VAD)-induced CS. Bioinformatics analysis and quantitative real-time PCR (qRT-PCR) indicated that SULT1C2A expression was down-regulated in VAD group, accompanied by increased expression of rno-miR-466c-5p but decreased expression of Foxo4 and somitogenesis-related genes such as Pax1, Nkx3-2 and Sox9 on gestational day (GD) 9. Luciferase reporter and small interfering RNA (siRNA) assays showed that SULT1C2A functioned as a competing endogenous RNA to inhibit rno-miR-466c-5p expression by direct binding, and rno-miR-466c-5p inhibited Foxo4 expression by binding to its 3' untranslated region (UTR). The spatiotemporal expression of SULT1C2A, rno-miR-466c-5p and Foxo4 axis was dynamically altered on GDs 3, 8, 11, 15 and 21 as detected by qRT-PCR and northern blot analyses, with parallel changes in Protein kinase B (AKT) phosphorylation and PI3K expression. Taken together, our findings indicate that SULT1C2A enhanced Foxo4 expression by negatively modulating rno-miR-466c-5p expression via the PI3K-ATK signalling pathway in the rat model of VAD-CS. Thus, SULT1C2A may be a potential target for treating CS. CI - (c) 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. FAU - Chen, Chong AU - Chen C AUID- ORCID: 0000-0003-1824-6116 AD - Department of Orthopedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. FAU - Tan, Haining AU - Tan H AD - Department of Orthopedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. FAU - Bi, Jiaqi AU - Bi J AD - Department of Orthopedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. FAU - Li, Lin AU - Li L AD - Beijing Zhongke Jingyun Technology Company Ltd., Beijing, China. FAU - Rong, Tianhua AU - Rong T AD - Department of Orthopedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. FAU - Lin, Youxi AU - Lin Y AD - Department of Orthopedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. FAU - Sun, Peiyu AU - Sun P AD - Department of Orthopedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. AD - Department of Orthopedics Surgery, Beijing Hospital of Traditional Chinese Medicine, Beijing, China. FAU - Liang, Jinqian AU - Liang J AD - Department of Orthopedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. FAU - Jiao, Yang AU - Jiao Y AD - Department of Orthopedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. FAU - Li, Zheng AU - Li Z AUID- ORCID: 0000-0001-6024-0194 AD - Department of Orthopedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. FAU - Sun, Liang AU - Sun L AD - Beijing Zhongke Jingyun Technology Company Ltd., Beijing, China. FAU - Shen, Jianxiong AU - Shen J AUID- ORCID: 0000-0002-1606-4370 AD - Department of Orthopedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190502 PL - England TA - J Cell Mol Med JT - Journal of cellular and molecular medicine JID - 101083777 RN - 0 (3' Untranslated Regions) RN - 0 (FOXO4 protein, rat) RN - 0 (Forkhead Transcription Factors) RN - 0 (MIRN466 microRNA, rat) RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - EC 1.13.12.- (Luciferases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - 3' Untranslated Regions/genetics MH - Animals MH - Base Sequence MH - Down-Regulation/genetics MH - Embryo, Mammalian/metabolism MH - Forkhead Transcription Factors/genetics/*metabolism MH - Gene Expression Regulation, Developmental MH - Genes, Reporter MH - HEK293 Cells MH - Humans MH - Luciferases/metabolism MH - MicroRNAs MH - Models, Biological MH - Organogenesis/genetics MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Proto-Oncogene Proteins c-akt/*metabolism MH - RNA, Long Noncoding/genetics/*metabolism MH - Rats, Sprague-Dawley MH - Scoliosis/*congenital/*genetics MH - *Signal Transduction MH - Somites/embryology MH - Vitamin A Deficiency/embryology/genetics PMC - PMC6584475 OTO - NOTNLM OT - Foxo4 OT - PI3K-AKT OT - SULT1C2A OT - congenital scoliosis (CS) OT - rno-miR-466c-5p OT - somitogenesis COIS- The authors confirm that there is no conflict of interest. EDAT- 2019/05/03 06:00 MHDA- 2020/08/07 06:00 PMCR- 2019/07/01 CRDT- 2019/05/03 06:00 PHST- 2019/02/23 00:00 [received] PHST- 2019/03/31 00:00 [revised] PHST- 2019/04/10 00:00 [accepted] PHST- 2019/05/03 06:00 [pubmed] PHST- 2020/08/07 06:00 [medline] PHST- 2019/05/03 06:00 [entrez] PHST- 2019/07/01 00:00 [pmc-release] AID - JCMM14355 [pii] AID - 10.1111/jcmm.14355 [doi] PST - ppublish SO - J Cell Mol Med. 2019 Jul;23(7):4582-4591. doi: 10.1111/jcmm.14355. Epub 2019 May 2.