Long noncoding RNA MIR22HG promotes Leydig cell apoptosis by acting as a competing endogenous RNA for microRNA-125a-5p that targets N-Myc downstream-regulated gene 2 in late-onset hypogonadism

Leydig cells (LCs) apoptosis is responsible for the deficiency of serum testosterone in Late-onset hypogonadism (LOH), while its specific mechanism is still unknown. This study focuses on the role of long noncoding RNA (lncRNA) MIR22HG in LC apoptosis and aims to elaborate its regulatory mechanism....

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Published in:Laboratory investigation 2021-11, Vol.101 (11), p.1484-1493
Main Authors: Liu, Yan-ling, Huang, Feng-jiao, Du, Pei-jie, Wang, Jiao, Guo, Feng, Shao, Ming-wei, Song, Yi, Liu, Yan-xia, Qin, Gui-jun
Format: Article
Language:English
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Adaptor Proteins, Signal Transducing - metabolism
Animal tissues
Animals
Apoptosis
Cell Line
Chromosome 5
Gene expression
Hydrogen peroxide
Hypogonadism
Hypogonadism - etiology
Leydig cells
Leydig Cells - physiology
Male
Mice
MicroRNAs - metabolism
MicroRNAs - physiology
miRNA
mRNA
Myc protein
Regulatory mechanisms (biology)
Ribonucleic acid
RNA
Testosterone
Testosterone - metabolism
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Summary:Leydig cells (LCs) apoptosis is responsible for the deficiency of serum testosterone in Late-onset hypogonadism (LOH), while its specific mechanism is still unknown. This study focuses on the role of long noncoding RNA (lncRNA) MIR22HG in LC apoptosis and aims to elaborate its regulatory mechanism. MIR22HG was up-regulated in the testicular tissues of mice with LOH and H2O2-treated TM3 cells (mouse Leydig cell line). Interference of MIR22HG ameliorated cell apoptosis and upregulated miR-125a-5p expression in H2O2-treated TM3 cells. Then, the interaction between MIR22HG and miR-125a-5p was confirmed with RIP and RNA pull-down assay. Further study showed that miR-125a-5p downregulated N-Myc downstream-regulated gene 2 (NDRG2) expression by targeting its 3′-UTR of mRNA. What's more, MIR22HG overexpression aggravated cell apoptosis and reduced testosterone production in TM3 cells via miR-125a-5p/NDRG2 pathway. MIR22HG knockdown elevated testosterone levels in LOH mice. In conclusion, MIR22HG up-regulated NDRG2 expression through targeting miR-125a-5p, thus promoting LC apoptosis in LOH. Leydig cell apoptosis is responsible for the deficiency in serum testosterone in late-onset hypogonadism. This study reveals that lncRNA MIR22HG upregulates NDRG2 expression by targeting miR-125a-5p, thus promoting Leydig cell apoptosis in late-onset hypogonadism.
ISSN:0023-6837
1530-0307
DOI:10.1038/s41374-021-00645-y