Exploring the dysregulated mRNAs–miRNAs–lncRNAs interactions associated to idiopathic non-obstructive azoospermia

Abstract

Non-obstructive azoospermia (NOA) is the most clinical problem in case of infertility. About 70% of NOA patients are idiopathic with uncharacterized molecular mechanisms. This study aimed to analyze the possible pathogenic miRNA–target gene interaction and lncRNA–miRNA association involved in NOA. In the current study, differentially expressed (DE) nRNAs, miRNAs and lncRNAs were determined using the microarray dataset and statistical software R. miRNAs–mRNA and miRNA–lncRNA interactions were identified and the base-pair binding between the seed region of miRNAs and complementary nucleotides in 3′ UTR of mRNAs were analyzed. The influence of the validated single nucleotide polymorphisms (SNPs) was described by calculating the minimum free energy (MFE) of the interaction. A total of 74 mRNAs, 14 miRNAs, and 10 lncRNAs were identified to have significant differential expression in testicular tissue between patients and the fertile group. Four of the DE-mRNAs and all of the reported DE-miRNAs were upregulated. In addition, all of the represented DE-lncRNAs were showed to be downregulated. miR-509-5p and miR-27b-3p were found to interact with target gene polo-like kinase 1 (PLK1) and Cysteine-rich secretory protein2 (CRISP2), respectively. Rs550967205 (A > G) positioned at 3′ UTR CRISP2 and rs544604911 (T > C) located at 3′ UTR PLK1, with lowest MFE in miRNA–mRNA interaction, were assumed to have possible pathogenic roles linked to spermatogenesis arrest. The results of the study provide new clues to understand the regulatory roles of miRNAs and lncRNAs in the pathogenesis and diagnosis of idiopathic azoospermia.

Communicated by Ramaswamy H. Sarma

Keywords:

• Idiopathic azoospermia
• mRNA
• miRNA
• lncRNA
• interaction
• differentially expressed gene

Disclosure statement

The authors declare that they have no conflicts of interest.

Ethical approval

The Medical Ethics Committee of Shiraz University of Medical Sciences approved the study protocol (Permission number: IR.SUMS.REC.1399.460).FundingThis study was financially supported by Vice Chancellor for Research of Shiraz University of Medical Sciences, Shiraz, Iran with the grant number of 99-01-106-22638.

Additional information

Funding

This study was supported by Vice-Chancellor of Research and Technology, Shiraz University of Medical Sciences with the grant number of 99-01-106-22638.