title: Single nucleotide polymorphism associated with nonsyndromic cleft palate influences the processing of miR-140.
abstract: Nonsyndromic oral cleft is a common developmental malformation of humans. Embryonic development is regulated by microRNAs. MicroRNA-140-5p (miR-140-5p) was found to regulate palatal development. As sequence variants in miRNA genes are likely to affect miRNA expression and/or maturation, we investigated the miRNA-140 gene and identified a SNP (rs7205289: C>A) located in precursor miRNA-140. We carried out a case-control analysis in 557 patients with nonsyndromic oral clefts and 306 unaffected controls from west China and found that the frequency of minor allele (A allele) was significantly increased (P = 0.003 after Bonferroni correction) in nonsyndromic cleft palate (NSCP) patients in comparison with that in controls. We constructed expression vectors of primary miRNA-140 (pri-miR-140) with the major and minor alleles of rs7205289. The vectors were transfected into HEK293 cells, and the mature forms of miR-140 were detected by Northern blot. Compared to the vector with the C allele, the vector with the A allele was found to influence the miR-140 processing, resulting in a significant decrease of miR-140-5p and an increase of miR-140-3p. These results suggest that the SNP located in pre-miR-140 contributes to NSCP susceptibility by influencing the processing of miR-140.
authors.affiliation: State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, Chengdu, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Tian
authors.initials: T
authors.lastname: Meng
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Jia
authors.forename: Guiquan
authors.initials: G
authors.lastname: Zhu
authors.forename: Bing
authors.initials: B
authors.lastname: Shi
mesh_terms: D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D002460:Cell Line; D002972:Cleft Palate / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012322:RNA Precursors / Q000235:genetics; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics; D014162:Transfection
chemical_list: D035683:MicroRNAs; C544302:Mirn140 microRNA, human; D012322:RNA Precursors