Functional Study of One Nucleotide Mutation in Pri-MiR-125a Coding Region which Related to Recurrent Pregnancy Loss
Autor: | Ning Zhang, Lu Qi, Xu Ma, Hong-Fei Xia, Zheng-Hao Huo, Yi Hu, Shiguo Liu, Chun-Mei Liu, Kun-Lun Yin |
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Jazyk: | angličtina |
Rok vydání: | 2014 |
Předmět: |
Abortion
Habitual RNA Stability Mutant lcsh:Medicine Biology medicine.disease_cause Biochemistry Polymorphism Single Nucleotide Molecular Genetics Endometrium Asian People Pregnancy microRNA Gene expression medicine Genetics Coding region Humans Genetic Predisposition to Disease lcsh:Science Gene 3' Untranslated Regions Cells Cultured Regulation of gene expression Mutation Multidisciplinary Biology and life sciences Three prime untranslated region lcsh:R MicroRNAs Mifepristone Gene Expression Regulation Haplotypes Case-Control Studies RNA lcsh:Q Female Stromal Cells Research Article |
Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 12, p e114781 (2014) |
ISSN: | 1932-6203 |
Popis: | MicroRNAs (miRNAs) are short non-coding RNAs which modulate gene expression by binding to complementary segments present in the 3′UTR of the mRNAs of protein coding genes. MiRNAs play very important roles in maintaining normal human body physiology conditions, meanwhile, abnormal miRNA expressions have been found related to many human diseases spanning from psychiatric disorders to malignant cancers. Recently, emerging reports have indicated that disturbed miRNAs expression contributed to the pathogenesis of recurrent pregnancy loss (RPL). In this study, we identified a new mutation site (+29A>G, position relative to pre-miR-125a) by scanning pri-miR-125a coding region in 389 Chinese Han RPL patients. This site was co-existed with two polymorphisms (rs12976445 and rs41275794) in patients heterogeneously and changed the predicted secondary structures of pri-miR-125a. Subsequent in vitro analysis indicated that the A>G mutation reduced mature miR-125a expression, and further led to less efficient inhibition of verified target genes. Functional analysis showed that mutant pri-mir-125a can enhance endometrial stromal cells (ESCs) invasive capacity and increase the sensitivity of ESCs cells to mifepristone. Moreover, we further analyzed the possible molecular mechanism by RIP-chip assay and found that mutant pri-mir-125a disturbed the expression of miR-125a targetome, the functions of which includes embryonic development, cell proliferation, migration and invasion. These data suggest that A>G mutation in pri-miR-125a coding region contributes to the genetic predisposition to RPL by disordering the production of miR-125a, which consequently meddled in gene regulatory network between mir-125a and mRNA. |
Databáze: | OpenAIRE |
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