Abstract：
Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a common craniofacial birth defect with complex etiologies. Recently, the dysregulation of long noncoding RNAs (lncRNAs) has been implicated in many developmental diseases, including NSCL/P. However, the functions and mechanisms of lncRNAs in NSCL/P have not been fully elucidated. In this study, we found that lncRNA MIR31HG in NSCL/P patients was significantly downregulated than that in healthy individuals (GSE42589, GSE183527). In addition, single nucleotide polymorphism rs58751040 in MIR31HG was nominally associated with NSCL/P susceptibility (odds ratio: 1.29, 95% confidence interval: 1.03-1.54, p = 4.93 × 10-2) through a case-control study (504 NSCL/P cases and 455 controls). Luciferase activity assay showed that the C allele of rs58751040 revealed a decreased transcription activity of MIR31HG than the G allele. Moreover, knockdown of MIR31HG promoted cell proliferation and migration in human oral keratinocytes and human embryonic palate mesenchyme. Bioinformatic analysis and cellular studies suggested that MIR31HG may confer susceptibility to risk of NSCL/P through matrix Gla protein (MGP) signaling. In summary, we identified a novel lncRNA involved in the development of NSCL/P.
摘要：
非综合征性唇裂伴或不伴腭裂（NSCL/P）是一种常见的颅面出生缺陷，病因复杂。最近,长链非编码RNA（lncRNAs）的失调与许多发育疾病有关，包括NSCL/P然而,lncRNAs在NSCL/P中的功能和机制尚未完全阐明。在这项研究中,我们发现NSCL/P患者的lncRNAMIR31HG比健康个体显著下调(GSE42589,GSE183527).此外,通过病例对照研究(504例NSCL/P病例和455例对照),MIR31HG中的单核苷酸多态性rs58751040与NSCL/P易感性名义上相关(比值比:1.29,95%置信区间:1.03-1.54,p=4.93×10-2)。荧光素酶活性分析表明，rs58751040的C等位基因显示MIR31HG的转录活性比G等位基因降低。此外，MIR31HG的敲低可促进人口腔角质形成细胞和人胚胎腭部间充质的细胞增殖和迁移。生物信息学分析和细胞研究表明，MIR31HG可能通过基质Gla蛋白（MGP）信号传导赋予NSCL/P的易感性。总之,我们鉴定了一种新的lncRNA参与NSCL/P的发展。
