Identification of male infertility-related long non-coding RNAs and their functions based on a competing endogenous RNA network

Abstract

Objective To identify male infertility-related long non-coding (lnc)RNAs and an lncRNA-related competing endogenous (ce)RNA network. Methods Expression data including 13 normospermic and eight teratozoospermic samples from postmortem donors were downloaded from the GEO database (GSE6872). The limma R package was used to discriminate dysregulated lncRNA and micro (m)RNA profiles. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of differentially expressed (DE) mRNAs were performed using the clusterProfiler R package. The ceRNA network of dysregulated genes was visualized by Cytoscape. Results A total of 101 DE lncRNAs and 1722 mRNAs were identified as male infertility-specific RNAs with thresholds of |log2FoldChange| >2.0 and adjusted P-value <0.05. GO and KEGG pathways were analyzed for DE mRNAs. Gene set enrichment analysis revealed that DE genes were enriched in embryonic skeletal system development and cytokine–cytokine receptor interactions. A ceRNA network was constructed with 26 key lncRNAs, 33 microRNAs, and 133 mRNAs. DE lncRNAs in male sterility were mainly associated with transferring phosphorus-containing groups and complexes of histone methyltransferases, methyltransferases, PcG proteins, and serine/threonine protein kinases. Conclusion This provides a novel perspective to study lncRNA-related ceRNA networks in male infertility and assist in identifying new potential biomarkers for diagnostic purposes.

The Role of Long Noncoding RNAs on Male Infertility: A Systematic Review and In Silico Analysis

“…It was found to be downregulated in two studies with NOA patients [ 27 , 29 ] and it is also deregulated in patients with asthenozoospermia [ 41 ], though no other publications are investigating its role or association with diseases. The same pattern is observed for lncRNA LINC00710, which is deregulated in NOA [ 27 ], oligozoospermia [ 37 ], and teratozoospermia [ 45 ]. This lncRNA is also highly expressed in the testis, but little information exists about its role or its involvement in specific cellular processes.…”

“…One more article was also excluded, as it was a perspective and did not present original data. Finally, a total of 20 articles remained to be included in the present systematic review [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ].…”

“…Then, the researchers constructed ceRNA networks with 26 key lncRNAs, 33 microRNAs, and 133 mRNAs. After GO and KEGG analysis, it was also found that differentially expressed lncRNAs were associated with transferring phosphorus-containing groups and complexes of histone methyltransferases, methyltransferases, PcG proteins, and serine/threonine protein kinases highlighting important processes for teratozoospermia [ 45 ].…”

“…In the studies included in the present systematic review, many more lncRNAs–miRNAs interactions that were detected through prediction models have been reported. Zhou and Wang (2020) [ 45 ] studied competing endogenous networks in teratozoospermia and found interactions between 26 key lncRNAs, 33 microRNAs, and 133 mRNAs ( Table S7 ). These interactions were also predicted with bioinformatic tools after the identification of differentially expressed mRNAs and lncRNAs.…”

“…COX10 antisense RNA 1 ( COX10-AS1 ) is another lncRNA that was found to be upregulated in patients with teratozoospermia [ 45 ] and asthenozoospermia [ 41 ], and is also deregulated in oligozoospermia [ 37 ]. Until now, little was known about the role of COX10-AS1 in human diseases; however, many studies associate it with human cancers as well.…”