Preliminary investigation of the function of hsa_circ_0049356 in nonobstructive azoospermia patients

Abstract

Nonobstructive azoospermia (NOA), which is considered the most severe form of male infertility, has placed a heavy burden on families and society. As vital regulators of transcriptional and post‐transcriptional levels, Noncoding RNAs (ncRNAs) are closely related to all the pathophysiological processes involved in infertility in males, especially spermatogenesis. Our study explored the expression levels of circ_0049356 in both the whole blood and seminal plasma samples of idiopathic NOA patients via quantitative real‐time PCR. Furthermore, the relative expression of its host gene (CARM1) was also determined using the same methods. In addition, as circRNAs have been demonstrated to regulate gene expression as miRNAs sponge, we predicted a total of five miRNAs and 101 mRNAs as putative downstream targets and constructed a circRNA‐miRNA‐mRNA network. Based on the predictions, Gene Ontology and KEGG pathway analyses were performed for further bioinformatics analysis to explore the potential function and investigate the circ_0049356‐miRNA‐mRNA interactions. Our results show target mRNAs that have been predicted to regulate guanyl‐nucleotide exchange factor activity to mediate the GTP/GDP exchange, and downstream targets possibly involved in the regulation of the actin cytoskeleton, which play a significant role in cytoskeleton rearrangement of germ cells during spermatogenesis.

Circular RNA regulates male spermatogenesis: a narrative review

“…Cai Y et al detected that circEIF3J and circPIAP2 can interact with small ribonucleoproteins in human cells, regulating host gene transcription in a cis-reaction manner [5]. (2) Circular RNA was mainly composed of exons; it may be involved in the generation of mRNA, and the formation of circular RNA can compete with linear mRNA [6]. However, this evidence did not support this hypothesis, such as a receptor site mutation in exon 4 or exon 5 of the flavin mononucleotide (fmn) gene, which can lead to corresponding circular RNA deletion but does not affect the splicing efficiency of linear RNA [7].…”

Circular RNAs and Their Role in Male Infertility: A Systematic Review

“…At the eligibility stage, we excluded four studies that did not report DE circRNAs. Finally, a total of 13 articles remained to be included in the present systematic review [36][37][38][39][40][41][42][43][44][45][46][47].…”

The gene regulatory role of non-coding RNAs in non-obstructive azoospermia

“…The expression of hsa-circRNA-0000116 in testicular tissue of patients with NOA is significantly higher than that in patients with OA, which affects fertility function through hsa_circ_0000116-miR-449-autophagy-related ceRNA network ( 83 ). Circ_0049356 participates in the regulation of actin cytoskeleton through circ_0049356-miRNA-mRNA pathway and plays an important role in the cytoskeleton rearrangement of germ cells during spermatogenesis ( 84 ). In addition, circRNA may regulate spermatogenesis by affecting the activity of SMAD protein in patients with NOA ( 85 ).…”