Haplotype‐based association of two SNPs in miR‐323b with unexplained recurrent spontaneous abortion in a Chinese Han population

다국어 초록 (Multilingual Abstract)

Single nucleotide polymorphisms (SNPs) in miRNAs are associated with the risk to development of certain human diseases and affect the regulatory capacity of miRNAs. However, the relationship between miRNAs polymorphisms and recurrent pregnancy loss (RPL) is still largely unknown. Our study found that one SNP rs56103835 T>C in miR‐323b coding region was associated with the increase risk of human unexplained RPL (URPL), but no differences were found in another SNP rs75330474 C>T. However, in two‐locus haplotype analysis, T‐C haplotype was associated with an increased risk of URPL. The level of mature miR‐323b was obviously up‐regulated in cells transfected with T‐C haplotype. T‐C haplotype inhibited HTR‐8/SVneo cells proliferation and migration and promoted cells apoptosis. Further experiments identified that paired‐box 8 (Pax8) was a functionally relevant target of miR‐323b, and its expression was reversely regulated by miR‐323b. Besides, the expressions of Pax8 in villous chorionic tissues from URPL patients were lower than controls, contrary to the high expression of miR‐323. More importantly, dual‐luciferase assay indicated T‐C haplotype, increasing miR‐323b expression, could down‐regulated Pax8 expression. Collectively, our data suggest that T‐C haplotype in pre‐miR‐323b may aggravate the risk of developing URPL and influence the level of mature miR‐323b and its target gene Pax8.
T‐C haplotype (constructed in rs56103835 T>C and rs75330474 C>T) was associated with an increased risk of unexplained recurrent pregnancy loss (URPL), obviously up‐regulated the expression of miR‐323b and inhibited HTR‐8/SVneo cells proliferation and migration and promoted cells apoptosis by functionally targeting paired‐box 8 (Pax8). We documented that T‐C haplotype in pre‐miR‐323b may aggravate the risk of developing URPL and influence the level of mature miR‐323b and its target gene Pax8 for the first time.