LncRNA‐SULT1C2A regulates Foxo4 in congenital scoliosis by targeting rno‐miR‐466c‐5p through PI3K‐ATK signalling

Abstract

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.

LINC00689 induces gastric cancer progression via modulating the miR‐338‐3p/HOXA3 axis

“…Long noncoding RNAs (lncRNAs) are longer than 200 nucleotides in the length, usually up to approximately 100 kb. 1,[13][14][15][16] LncRNAs have showed to be deregulated in many tumors, such as hepatocellular carcinoma, lung cancer, nasopharyngeal carcinoma, breast cancer and gastric cancer. [17][18][19][20][21][22] More studies have suggested that lncRNAs play a functional role in several biological processes, such as cell development, proliferation, invasion, apotosism, stem cell pluripotency and differentiation.…”

“…Long noncoding RNAs (lncRNAs) are longer than 200 nucleotides in the length, usually up to approximately 100 kb 1,13–16 . LncRNAs have showed to be deregulated in many tumors, such as hepatocellular carcinoma, lung cancer, nasopharyngeal carcinoma, breast cancer and gastric cancer 17–22 .…”

Emerging roles of non‐coding RNAs in scoliosis

“…Our team has shown that embryonic expression of the lncRNA SULT1C2A was decreased whereas miR-466c-5p was upregulated in the rat model of vitamin A deficiency-induced congenital scoliosis. 43 Somitogenesis-related genes, such as Foxo4, Sox9, Pax1 and Nkx3-2, were downregulated on gestational day 9 upon maternal vitamin A deficiency. In this regard, reduced expression of SULT1C2A was found F I G U R E 1 Pathogenic mechanism of deregulated ncRNAs in scoliosis to increase the availability of miR-466c-5p and thereby decreasing…”

“…Our team has shown that embryonic expression of the lncRNA SULT1C2A was decreased whereas miR‐466c‐5p was upregulated in the rat model of vitamin A deficiency‐induced congenital scoliosis . Somitogenesis‐related genes, such as Foxo4, Sox9, Pax1 and Nkx3‐2, were downregulated on gestational day 9 upon maternal vitamin A deficiency.…”

HIX003209 promotes vascular smooth muscle cell migration and proliferation through modulating miR-6089

“…Growing studies demonstrated that lncRNAs played roles in several cellular functions such as cell apoptosis, differentiation and proliferation [18][19][20][21][22]. LncRNAs were also deregulated in multiple diseases including tumors, coronary heart disease, scoliosis and intervertebral disc degeneration [23][24][25][26]. Recently, a new lncRNA HIX003209 has been identified and found to be invovled in the development of rheumatoid arthritis [27].…”