Comparative Transcriptome Analyses of Geriatric Rats Associate Age-Related Erectile Dysfunction With a lncRNA-miRNA-mRNA Regulatory Network

老年大鼠的比较转录组分析将年龄相关性勃起功能障碍与 lncRNA-miRNA-mRNA 调控网络联系起来

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作者:Xuan Zhou, Rong Cong, Liangyu Yao, Xiang Zhou, Jiaochen Luan, Qijie Zhang, Xu Zhang, Xiaohan Ren, Tongtong Zhang, Xianghu Meng, Ninghong Song

Aim

This study aimed to identify putative lncRNAs that regulate age-related erectile dysfunction via transcriptome analyses, and to predict their specific regulatory routes via bioinformatics

Background

The key regulatory roles of long non-coding RNAs (lncRNAs) in age-related erectile dysfunction (A-ED) are unknown.

Conclusion

Our study identified differentially expressed lncRNAs, miRNAs, and mRNAs through comparisons of transcriptomes of geriatric rats. An identified lncRNA verified by qPCR, was used to construct a lncRNA-miRNA-mRNA regulatory network. LncRNA ENSRNOT00000029245 possibly regulated downstream mRNAs through this regulatory network, leading to apoptosis in the cavernous tissue, fibrosis, and endothelial dysfunction, which ultimately caused ED. These findings provide seminal insights into the molecular biology of aging-related ED, which could spur the development of effective therapeutics.

Methods

22 geriatric male SD rats were divided into age-related erectile dysfunction (A-ED) and negative control (NC) groups after evaluations of intracavernous pressure (ICP). By comparative analysis of transcriptomes of cavernosal tissues from both groups, we identified differentially expressed lncRNAs, miRNAs, and mRNAs. Seven differentially expressed lncRNAs were selected and further verified by quantitative real-time polymerase chain reactions (RT-qPCR). The construction of the lncRNA-miRNA-mRNA network, the Gene Ontology (GO) term enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in Cytoscape.

Results

From comparative transcriptome analyses of A-ED and NC groups, 69, 29, and 364 differentially expressed lncRNAs, miRNAs, and mRNAs were identified respectively. Differentially expressed lncRNAs were culled to seven, which were all verified by qPCR. Three of these lncRNAs (ENSRNOT00000090050, ENSRNOT00000076482, and ENSRNOT00000029245) were used to build regulatory networks, of which only ENSRNOT00000029245 was successful. Moreover, GO and KEGG analyses demonstrated that these lncRNAs possibly regulated muscle myosin complex, muscle cell cellular homeostasis, and ultimately erectile function in rats through PI3K-Akt, fluid shear stress, and atherosclerosis pathways.

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