lncRNA Regulates Proliferation and Migration by Targeting Matrix Gla Protein in Nonsyndromic Cleft Lip With or Without Cleft Palate.

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 in NSCL/P patients was significantly downregulated than that in healthy individuals (GSE42589, GSE183527). In addition, single nucleotide polymorphism rs58751040 in was nominally associated with NSCL/P susceptibility (odds ratio: 1.29, 95% confidence interval: 1.03-1.54,  = 4.93 × 10) 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 than the G allele. Moreover, knockdown of promoted cell proliferation and migration in human oral keratinocytes and human embryonic palate mesenchyme. Bioinformatic analysis and cellular studies suggested that may confer susceptibility to risk of NSCL/P through matrix Gla protein () signaling. In summary, we identified a novel lncRNA involved in the development of NSCL/P.