Oncotarget

Research Papers:

A SNP in pri-miR-10a is associated with recurrent spontaneous abortion in a Han-Chinese population

Ying Li, Xue-Qin Wang, Lu Zhang, Xiao-Dan Lv, Xing Su, Shi Tian, Chun-Mei Liu, Xu Ma _ and Hong-Fei Xia

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Oncotarget. 2016; 7:8208-8222. https://doi.org/10.18632/oncotarget.7002

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Abstract

Ying Li1,2,*, Xue-Qin Wang1,2,*, Lu Zhang1,2, Xiao-Dan Lv1,2, Xing Su1,2, Shi Tian3, Chun-Mei Liu1,2, Xu Ma1,2, Hong-Fei Xia1,2

1Reproductive and Genetic Center of National Research Institute for Family Planning, Beijing, China

2Graduate School, Peking Union Medical College, Beijing, China

3Haidian Maternal & Child Health Hospital, Beijing, China

*These authors have contributed equally to this work

Correspondence to:

Xu Ma, e-mail: genetic@263.net.cn

Hong-Fei Xia, e-mail: hongfeixia@126.com

Keywords: miR-10a, recurrent spontaneous abortion, haplotype, rs3809783

Received: June 17, 2015     Accepted: January 01, 2016     Published: January 25, 2016

ABSTRACT

MicroRNA-10a (miR-10a) has a wide range of functions in nearly all mammalian tissues and is involved in the occurrence of many diseases. However, it remains unknown whether miR-10a is associated with human recurrent spontaneous abortion (RSA). In this study, we found that rs3809783 A > T in miR-10a coding region was significantly associated with the increase of the risk of human unexplained RSA (URSA) acquisition in a Han-Chinese population. The T allele of rs3809783 hindered the production of mature miR-10a. A to T substitution in miR-10a rs3809783 repressed cell proliferation and migratory capacity. Further investigation discovered that Bcl-2-interacting mediator (Bim) was the functional target of miR-10a and inversely regulated Bim expression. Dual-luciferase assay indicated that A allele in miR-10a rs3809783 could more effectively suppress Bim expression than T allele. In addition, A to T substitution in miR-10a rs3809783 attenuated the sensibility of cells to progesterone and its antagonist mifepristone. Collectively, our data suggest that rs3809783 A > T in pri-miR-10a may be conductive to the genetic predisposition to RSA by disrupting the production of mature miR-10a and reinforcing the expression of Bim.


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