Upregulated lncRNA Gm2044 inhibits male germ cell development by acting as miR-202 host gene

Anim Cells Syst (Seoul). 2019 Mar 14;23(2):128-134. doi: 10.1080/19768354.2019.1591506. eCollection 2019 Apr.

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.

Keywords: Gm2044; LncRNA; miR-202; non-obstructive azoospermia.

Grants and funding

This study was funded by the National Natural Science Foundation of China (81801516), the Natural Science Foundation of Anhui Province (China) (1608085QH199), and the Key Project of Natural Science Foundation of Anhui Provincial Department of Education (China) (KJ2018A0992).