The polymorphism of rs11614913 T/T in pri-miR-196a-2 alters the miRNA expression and associates with recurrent spontaneous abortion in a Han-Chinese population.

Rs11614913 in pri-miR-196a-2 is involved in the occurrence of many diseases, especially in cancers. However, it remains unknown whether miR-196a-2 is associated with human recurrent spontaneous abortion (RSA) in Chinese Han population. Our study found that rs11614913 T/T in pri-miR-196a-2 was associated with the increase risk of human unexplained RSA (URSA) in recessive mode in Chinese Han population. The T allele of rs11614913 increased the production of mature miR-196a-3p. Rs11614913 T/T inhibited HTR-8/SVneo cells proliferation and migration and promoted cells apoptosis. Further investigation discovered that dihydrofolate reductase (DHFR) was the target of miR-196a-3p and inversely regulated by miR-196a-3p. Dual-luciferase assay indicated that T allele in miR-196a-2 rs11614913 could more effectively suppress DHFR expression than C allele. In addition, C to T substitution in miR-196a-2 rs11614913 attenuated the sensibility of cells to mifepristone. Collectively, our data suggest that miR-196a-2 rs11614913 T/T in pri-miR-196a-2 may be conductive to the genetic predisposition to RSA by disrupting the production of mature miR-196a-3p and reinforcing the expression of DHFR.