Functional study of one nucleotide mutation in pri-miR-125a coding region which related to recurrent pregnancy loss.
Functional study of one nucleotide mutation in pri-miR-125a coding region which related to recurrent pregnancy loss.
复制标题
pri-miR-125a编码区一个核苷酸突变与复发性流产相关的功能研究。
DOI：
10.1371/journal.pone.0114781
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Xia HF
中科院分区：
文献类型：
--
作者：
Hu Y;Huo ZH;Liu CM;Liu SG;Zhang N;Yin KL;Qi L;Ma X;Xia HF
microRNA（miRNAs）是一类短的非编码RNA，通过与蛋白质编码基因mRNA的3′UTR互补片段结合来调控基因表达。微小RNA在维持人体正常生理状态方面发挥着非常重要的作用，同时发现微小RNA的异常表达与从精神疾病到恶性肿瘤等多种人类疾病有关。最近，新的报告表明，干扰的miRNAs表达有助于复发性妊娠丢失（RPL）的发病机制。本研究通过对389例中国汉族RPL患者的pri-miR-125 a编码区进行扫描，发现了一个新的突变位点（+29A>G，相对于pre-miR-125 a的位置）。该位点与两个多态性（rs 12976445和rs 41275794）在患者中不均匀地共存，并改变了pri-miR-125 a的预测二级结构。随后的体外分析表明，A>G突变降低了成熟miR-125 a的表达，并进一步导致对验证的靶基因的抑制效率降低。功能分析显示，突变型pri-mir-125 a能增强子宫内膜基质细胞（ESCs）的侵袭能力，并增加ESCs对米非司酮的敏感性。此外，我们还通过RIP-chip分析了其可能的分子机制，发现突变的pri-mir-125 a干扰了miR-125 a targetome的表达，其功能包括胚胎发育、细胞增殖、迁移和侵袭。这些数据表明pri-miR-125 a编码区的A>G突变通过扰乱miR-125 a的产生，从而干扰mir-125 a和mRNA之间的基因调控网络，从而导致RPL的遗传易感性。
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.
登录
查看更多内容
DOI：
10.1016/s0950-3552(05)80077-x
发表时间：
1991-03-01
期刊：
BAILLIERES CLINICAL OBSTETRICS AND GYNAECOLOGY
影响因子：
--
作者：
CHARD, T
通讯作者：
CHARD, T
影响因子：
4.5
作者：
Easow, George;Teleman, Aurelio A.;Cohen, Stephen M.
通讯作者：
Cohen, Stephen M.
DOI：
10.1073/pnas.0802682105
发表时间：
2008-05-20
影响因子：
11.1
作者：
Jazdzewski, Krystian;Murray, Elizabeth L.;de la Chapelle, Albert
通讯作者：
de la Chapelle, Albert
影响因子：
6.7
作者：
Li, AM;Felix, JC;Jain, JK
通讯作者：
Jain, JK
影响因子：
3.9
作者：
Hoy AM;Buck AH
通讯作者：
Buck AH