CircRNA expression profile and functional analysis in testicular tissue of patients with non-obstructive azoospermia

Abstract

BackgroundNon-obstructive azoospermia (NOA) is a multifactorial disorder whose molecular basis remains largely unknown. Circular RNAs (CircRNAs), a novel class of endogenous RNAs, have been recognized to play important roles in many biological processes. However, little is known about the expression patterns and functions of circRNAs in human testes involved in NOA.MethodsIn this study, the testicular circRNA expression profile were explored in NOA patients and the controls by high-throughput circRNA microarray. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to confirm the microarray data. Bioinformatics analyses including the circRNA/miRNA/mRNA interaction network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to predict the functions of differentially expressed circRNAs.ResultsA total of 368 differentially down-regulated and 526 up-regulated circRNAs were detected in NOA patients. These findings have been verified by qRT-PCR on 6 selected circRNAs. Among these differentially expressed circRNAs, the hsa_circRNA_0023313 was obviously up-regulated in testicular tissue of NOA patients. The most likely potential target miRNA for hsa_circRNA_0023313 include hsa-miR-520d-3p, hsa-miR-373-3p, hsa-miR-372-3p, hsa-miR-302c-3p and hsa-miR-130b-5p. Function analysis indicated that hsa_circRNA_0023313 was ubiquitin-protein transferase activity and chromatin binding. KEGG analysis revealed that the top five pathways related to hsa_circRNA_0023313 were endocytosis, meiosis, FoxO signaling pathway, ubiquitin mediated proteolysis and AMPK signaling pathway.ConclusionsThis is the first report that the testicular circRNA expression profile is altered in NOA patients indicating circRNAs might play important roles in regulating spermatogenesis and be potential biomarkers for the diagnosis and treatment of NOA.

Over‐expression of hsa_circ_0000116 in patients with non‐obstructive azoospermia and its predictive value in testicular sperm retrieval

“…Dong et al predicted that there are 15,996 circRNAs expressed in a healthy human testis, which regulates gene expressions in spermatogenesis 33 . Our earlier microarray results 23 also revealed that a total of 368 differentially down‐regulated and 526 up‐regulated circRNAs were detected in NOA patients, further indicating that circRNAs might be playing major roles in regulating spermatogenesis 36 …”

“…33 Compared with linear RNAs, circRNAs may have a higher representation in eukaryotic transcriptome 35 expressions in spermatogenesis. 33 Our earlier microarray results 23 also revealed that a total of 368 differentially down-regulated and 526 up-regulated circRNAs were detected in NOA patients, further indicating that circRNAs might be playing major roles in regulating spermatogenesis. 36 The hsa_circ_0000116, located in chromosome 1, is an exonic circRNA.…”

“…21,22 However, their association with male infertility is still largely unknown. Among the thousands of circRNAs in humans, hsa_circ_0000116 was selected for this study, based on the finding of our earlier cir-cRNA microarray study 23 where hsa_circ_0000116 showed high expression in infertile patients compared to that in the control group. The current study aimed to investigate the possible role of hsa_circ_0000116 in NOA and to define the relationships between its expression level and clinical-pathological parameters such as age, testicular volume, serum hormone level, pathological pattern, and Johnsen score in NOA patients.…”

Weighted Correlation Gene Network Analysis Reveals New Potential Mechanisms and Biomarkers in Non-obstructive Azoospermia

“…In the study of Ge et al, it was found that circRNA related to NOA is also involved in the regulation of FoxO signaling pathway. It shows that FoxO pathway is a key pathway of NOA ( Ge et al, 2019 ). In the pathway analysis, a pathway similar to T-cell leukemia virus 1 was also enriched.…”

Preliminary investigation of the function of hsa_circ_0049356 in nonobstructive azoospermia patients

“…Ge et al. (2019) and Bo et al. (2020) compared the expression profiles of specific circRNAs in the testes of OA and NOA patients, but the differential expression of circRNAs in blood and seminal plasma was not mentioned.…”