Rs2262251 in lncRNA RP11‐462G12.2 is associated with nonsyndromic cleft lip with/without cleft palate

Abstract

Nonsyndromic cleft lip with/without cleft palate (NSCL/P) is one of the most common human congenital defects. Rs2262251 (G>C) in long noncoding RNA (lncRNA) RP11‐462G12.2 is in high linkage disequilibrium with rs8049367, which was identified in our previous genome‐wide association study on NSCL/P, and is a potential causative single‐nucleotide polymorphism (SNP) for NSCL/P. To test these hypotheses, rs2262251 was evaluated in another cohort of 1,314 cases and 1,259 controls. Rs2262251 was associated with NSCL/P risk (p = .003). However, no association was detected for cleft palate only. SNP rs2262251 affected the structure and expression of lncRNA RP11‐462G12.2 in HEK293 and HEPM cells and in lip tissues from patients with NSCL/P. Overexpression of the rs2262251 G allele contributed to reducing the number of cells in the G0/G1 phase, inhibiting cell apoptosis, and promoting cell proliferation in vitro. The rs2262251 C allele regulated the expression of miR‐744‐5p and its target gene IQSEC2, both of which were expressed in human lip tissues, and showed reverse correlation during mouse lip development. Taken together, these findings suggest that rs2262251 is associated with the risk of NSCL/P and participates in a lncRNA–miRNA–mRNA regulatory axis in which miR‐744‐5p and IQSEC2 combine to control NSCL/P development.

Functional identification of a rare vascular endothelial growth factor a ( VEGFA ) variant associating with the nonsyndromic cleft lip with/without cleft palate

“…The human embryonic palatal mesenchyme (HEPM) cells have been widely applied to the study of palatal growth and development [ 17 , 18 ]. The human embryonic kidney 293 (HEK-293) cells have been often used to study cell function [ 19 ].…”

Long non‐coding RNAs MALAT1 and NEAT1 in non‐syndromic orofacial clefts

“…Similarly, in rats, the ceRNA NONMMUT004850.2‐NONMMUT024276.2‐miR‐741‐3p‐miR‐465b‐5p‐Prkar1α is an important regulator of palate fusion (Shu, Dong, Zhang, & Shu, 2019). Studying pathogenic single nucleotide polymorphisms (SNPs) has shown that rs2262251 is related to NSOFC via ceRNA networks (RP11/462G12.2‐miR‐744‐5p/IQSEC2) (Yun, 2019).…”

SP1-Mediated Upregulation of Long Noncoding RNA ZFAS1 Involved in Non-syndromic Cleft Lip and Palate via Inactivating WNT/β-Catenin Signaling Pathway

“…They have also been shown to participate in the development of lip and palate and the pathogenesis of related diseases ( Gerrard et al, 2016 ; Gao et al, 2019 ; Shu et al, 2019 ). There have been a few of reports on the role of lncRNAs in CLP ( Uslu et al, 2014 ; Gao et al, 2017 ; Yun et al, 2019 ), let alone NSCLP. RNA sequencing to identify transcriptome profiles including mRNAs, lncRNAs, and microRNAs (miRNAs) in NSCLP was performed in 2019 for the first time, and the potential role of lncRNAs in NSCLP has been suggested ( Gao et al, 2019 ).…”

“…RNA sequencing to identify transcriptome profiles including mRNAs, lncRNAs, and microRNAs (miRNAs) in NSCLP was performed in 2019 for the first time, and the potential role of lncRNAs in NSCLP has been suggested ( Gao et al, 2019 ). So far, only several lncRNAs have been identified to be associated with NSCLP in previous studies, including lncRNA RP11-462G12.2, CCDC26 lncRNA, and a long non-coding interval at 8q24 ( Uslu et al, 2014 ; Wu et al, 2019 ; Yun et al, 2019 ). Therefore, the underlying mechanism and function of lncRNAs in the involvement of NSCLP remain largely unclear.…”