Journal
HUMAN MUTATION
Volume 40, Issue 11, Pages 2057-2067Publisher
WILEY-HINDAWI
DOI: 10.1002/humu.23859
Keywords
long noncoding RNA; miRNAs; molecular genetics; nonsyndromic cleft lip with; without cleft palate; polymorphism
Categories
Funding
- Jiangsu Provincial Key Medical Discipline [zdxka2016026]
- Natural Science Foundation of Jiangsu Province [BL2014073, 15KJA320002]
- State Key Lab of Reproductive Medicine of Nanjing Medical University [JX116GSP20171416]
- Priority Academic Program Development of Jiangsu Higher Education Institutions [PAPD-2014-37]
- Jiangsu Provincial Medical Talent [ZDRCC2016023]
- Qing Lan Project
- Six Distinguished Talent [2016-WSW-008]
- National Natural Science Foundation of China [81570959, 81830031]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available