Upregulated lncRNA Gm2044 inhibits male germ cell development by acting as miR-202 host gene
Upregulated lncRNA Gm2044 inhibits male germ cell development by acting as miR-202 host gene
复制标题
上调lncRNA Gm2044通过充当miR-202宿主基因抑制雄性生殖细胞发育
DOI：
10.1080/19768354.2019.1591506
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发表时间：
2019-03-04
影响因子：
2.9
通讯作者：
Liao, Yaping
中科院分区：
文献类型：
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作者：
Liang, Meng;Hu, Ke;Liao, Yaping
摘要长链非编码RNA（lncRNA）参与了人类生精细胞发育的调控。然而，对与生精障碍相关的lncRNA的异常表达及其分子机制知之甚少。利用男性不育睾丸组织lncRNA微阵列和生物信息学方法，我们筛选出了在非梗阻性无精子症中可能起重要作用的相对保守的lncRNA Gm 2044。UCSC基因组浏览器显示lncRNA Gm 2044是miR-202宿主基因。本研究揭示了lncRNA Gm 2044和miR-202在精原细胞阻滞的非阻塞性无精子症中显著增加。Rbfox 2是miR-202的已知直接靶基因，其mRNA和蛋白水平受lncRNA Gm 2044调控。此外，miR-202-Rbfox 2信号通路显示介导lncRNA Gm 2044对人睾丸胚胎癌细胞增殖的抑制作用。了解lncRNA调控精子发生的分子信号通路将为男性不育患者的发病机制和治疗提供新的线索。
ABSTRACT Long non-coding RNAs (lncRNAs) have been found to participate in the regulation of human spermatogenic cell development. However, little is known about the abnormal expression of lncRNAs associated with spermatogenic failure and their molecular mechanisms. Using lncRNA microarray of testicular tissue for male infertility and bioinformatics methods, we identified the relatively conserved lncRNA Gm2044 which may play important roles in non-obstructive azoospermia. The UCSC Genome Browser showed that lncRNA Gm2044 is the miR-202 host gene. This study revealed that lncRNA Gm2044 and miR-202 were significantly increased in non-obstructive azoospermia of spermatogonial arrest. The mRNA and protein levels of Rbfox2, a known direct target gene of miR-202, were regulated by lncRNA Gm2044. Furthermore, the miR-202-Rbfox2 signalling pathway was shown to mediate the suppressive effects of lncRNA Gm2044 on the proliferation of human testicular embryonic carcinoma cells. Understanding of the molecular signalling pathways for lncRNA-regulated spermatogenesis will provide new clues into the pathogenesis and treatment of patients with male infertility.