The polymorphism of rs6505162 in the MIR423 coding region and recurrent pregnancy loss.
Although the relationship between polymorphisms in microRNAs (miRNAs) and recurrent pregnancy loss (RPL) has been studied, there is very little data available in the literature. In the present study, we scanned 55 potentially functional polymorphisms in the miRNA coding region in Chinese women with unexplained RPL (URPL; no. 2011-10). The rs6505162 C>A in the MIR423 coding region was found to be significantly associated with the occurrence of human URPL. The rare A allele contributed to an increase in the expression of mature MIR423. C to A substitution in the polymorphism rs6505162 in pre-MIR423 repressed cell proliferation and migratory capacity. Further investigations showed that MIR423 could inversely regulate the expression of proliferation-associated 2 group 4 (PA2G4) by binding the 3'-UTR of PA2G4. Dual-luciferase assay indicated that the A allele in the polymorphism rs6505162 could more effectively suppress the expression of PA2G4 than the C allele could. Collectively, the present data suggest that rs6505162 C>A in pre-MIR423 may contribute to the genetic predisposition to RPL by disrupting the production of mature MIR423 and its target gene, which consequently interferes with MIR423 functioning.
Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China.
Xing
X
Su
Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China.
Yi
Y
Hu
Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China.
Ying
Y
Li
Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China.
Jing-Li
JL
Cao
Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China.
Xue-Qin
XQ
Wang
Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China genetic@126.com hongfeixia@126.com.
Xu
X
Ma
Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China Reproductive and Genetic Center of National Research Institute for Family PlanningBeijing 100081, ChinaGraduate SchoolPeking Union Medical College, Beijing, China genetic@126.com hongfeixia@126.com.
Hong-Fei
HF
Xia
D000026:Abortion, Habitual / Q000235:genetics*; D000483:Alleles; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy
C548900:MIRN423 microRNA, human; D035683:MicroRNAs