环状 RNA 表达谱及在非梗阻性无精子症患者睾丸组织中的功能分析。
CircRNA expression profile and functional analysis in testicular tissue of patients with non-obstructive azoospermia.
机构信息
Department of Pathology, Medical School, Xi'an Jiaotong University, Xi'an, 710061, China.
Research Center of Reproductive Medicine, Medical School, Xi'an Jiaotong University, Xi'an, 710061, China.
出版信息
Reprod Biol Endocrinol. 2019 Nov 27;17(1):100. doi: 10.1186/s12958-019-0541-4.
BACKGROUND
Non-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.
METHODS
In 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.
RESULTS
A 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.
CONCLUSIONS
This 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.
背景
非阻塞性无精子症（NOA）是一种多因素疾病，其分子基础在很大程度上尚不清楚。环状 RNA（CircRNAs）作为一类新的内源性 RNA，已被证实在许多生物学过程中发挥重要作用。然而，关于涉及 NOA 的人睾丸中 circRNAs 的表达模式和功能知之甚少。
方法
本研究通过高通量 circRNA 微阵列探讨了 NOA 患者和对照者的睾丸 circRNA 表达谱。实时定量逆转录聚合酶链反应（qRT-PCR）用于验证微阵列数据。生物信息学分析包括 circRNA/miRNA/mRNA 相互作用网络、基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析，用于预测差异表达 circRNAs 的功能。
结果
在 NOA 患者中检测到 368 个差异下调和 526 个上调的 circRNAs。通过对 6 个选定的 circRNAs 进行 qRT-PCR 验证了这些发现。在这些差异表达的 circRNAs 中，hsa_circRNA_0023313 在 NOA 患者睾丸组织中明显上调。hsa_circRNA_0023313 的最可能潜在靶 miRNA 包括 hsa-miR-520d-3p、hsa-miR-373-3p、hsa-miR-372-3p、hsa-miR-302c-3p 和 hsa-miR-130b-5p。功能分析表明，hsa_circRNA_0023313 具有泛素-蛋白转移酶活性和染色质结合。KEGG 分析显示，与 hsa_circRNA_0023313 相关的前 5 个途径是内吞作用、减数分裂、FoxO 信号通路、泛素介导的蛋白水解和 AMPK 信号通路。
结论
这是首次报道睾丸 circRNA 表达谱在 NOA 患者中发生改变，表明 circRNAs 可能在调节精子发生中发挥重要作用，并可能成为 NOA 诊断和治疗的潜在生物标志物。
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