New insights into the expression profile of MicroRNA-34c and P53 in infertile men spermatozoa and testicular tissue

Abstract

Spermatogenesis is proliferation and differentiation processes of stem spermatogonia into mature spermatozoa controlled by the genes responsible for transcription and post transcription levels. MicroRNAs (miRNA) are the key factors during gene expression in RNA silencing and post-transcriptional regulation. They play main roles in regulation of early and late spermatogenesis, and reproduction. In this study, we investigate the role of miRNAs in infertile males.The patients were assigned to five groups based on semen analysis (n=55), including normozoospermic (N), moderate oligoasthenoteratozoospermic (MOAT), severe oligoasthenoteratozoospermic (SOAT), obstructive azoospermia (OA) and non-obstructive azoospermia (NOA). Quantitative RT-PCR was recruited to study the expression of miR-34c and tumor suppressor p53 gene. In addition, malondialdehyde (MDA) and DNA fragmentation was measured. Network analysis was performed using Pathway Studio web tool (Elsevier). Our results revealed statistically significant increased expression of miR-34c in moderate oligoasthenoteratozoospermic, non-obstructive azoospermia and an increased expression of p53 in MOAT, SOAT and NOA males. Also, the percentage of DNA fragmentation and oxidative stress was significantly higher in infertile groups (MOAT and SOAT) than other groups. These findings provide a novel molecular mechanism of gene regulation during cell-cycle and apoptosis in sperm, which gives a new regulatory insight into male infertility in terms of molecular diagnosis.

The human amniotic fluid mesenchymal stem cells therapy on, SKOV3, ovarian cancer cell line

“…Wild type p53 locus on 17p13.1 has been indicated to be an inhibitor of cancer cells proliferation by controlling cell cycle at Go to G1 passing, G2 checkpoint and G2/M passing (Rahbar et al, 2017). At G1 to S phase inhibition mediated by p21 that stimulated its activities with p53 (Innocente, Abrahamson, Cogswell, & Lee, 1999;Lamb & Crawford, 1986).…”

Microarray meta‐analysis identifies candidate genes for human spermatogenic arrest

“…Some of the hub genes presented in our results have been previously reported in spermatogenesis studies. In particular, the transcript of TP53 (p53), which had the second‐highest degree in pre‐meiotic arrest, has been confirmed to be elevated in some infertile testes in human patients compared with normal values (Rahbar et al, ; Jaiswal et al, ). These findings together with our results present the possibility that p53 may contribute to the cell cycle suppression in pre‐meiotic arrest.…”

“…p53 has recently been reported to be dramatically increased in the testes of infertile patients, including NOA patients (Rahbar et al, ; Jaiswal et al, ). p53 mainly functions as a guardian of DNA integrity by mediating DNA damage recovery or activating the apoptosis process.…”

“…Subsequently, bioinformatics analyses were performed (including Gene Ontology [GO], pathway enrichment analysis, protein–protein interaction [PPI] network analysis and expression profile determination of cell cycle‐associated genes) to obtain overviews of major biological events and hub genes. Finally, we focused on hub gene TP53 (p53), which was previously reported to be overexpressed in nonobstructive azoospermia (NOA; Jaiswal et al, ; Rahbar et al, ), and screened out the p53‐interacting proteins during pre‐meiotic arrest to identify new candidate genes for further analysis.…”

Non‐coding and coding genomic variants distinguish prostate cancer, castration‐resistant prostate cancer, familial prostate cancer, and metastatic castration‐resistant prostate cancer from each other

“…55 It is predicted that nearly sixty percent of all protein-coding genes may be regulated by microRNAs. 9,56 Considering the high stability of microRNAs in blood, their abnormal expression as tumor suppressors or as oncogenes offers a new class of cancer predictive biomarkers. 1,31,57 The frequent occurrence of prostate cancer-associated variants in 3′UTRs suggests the importance of noncoding regulatory variants in different types of prostate cancer; the area that has been neglected compared with coding variants.…”