基于microRNA与生物信息学筛选非梗阻性无精子症的生物标志物

doi:10.16288/j.yczz.25-089

遗传 ›› 2026, Vol. 48 ›› Issue (3): 301-312.doi: 10.16288/j.yczz.25-089

基于microRNA与生物信息学筛选非梗阻性无精子症的生物标志物

李志宏¹(), 陈淼琪¹(), 袁晓珺¹, 黄华君¹, 黄琬婷¹, 周飘雁¹, 曾晨¹, 冯许诺¹, 杨洛瑶¹, 黄树强¹, 谭翠钰¹, 陈彩蓉¹^,², 颜秋霞¹^,²()

1.广州医科大学附属清远医院，清远市人民医院生殖医学中心，清远 511518
2.广东省尿控及生殖医学创新工程技术研究中心，清远 511518

收稿日期:2025-07-02 修回日期:2025-10-24 出版日期:2026-03-20 发布日期:2025-10-30
通讯作者: 颜秋霞，博士，主任技师/研究员，研究方向：生殖医学。E-mail: yqx2168@163.com
作者简介:李志宏，本科在读，专业方向：临床医学。E-mail: lizhihong5198@outlook.com;
陈淼琪，本科在读，专业方向：临床医学。E-mail: cmqmq0502@163.com
第一联系人：
李志宏和陈淼琪并列第一作者。
基金资助:
广东省基础与应用基础研究基金(2025A1515012629);广东省基础与应用基础研究基金(2023A1515220129);广东省基础与应用基础研究基金(2019A1515010249);广东省中医药局科研项目(20241387);广州医科大学附属清远医院(清远市人民医院)开放课题基金(202301-306);广州医科大学附属清远医院(清远市人民医院)开放课题基金(202301-104);广州医科大学创新能力提升计划项目(240603131131);广州医科大学创新能力提升计划项目(240603131129);广东省大学生创新训练计划项目(S202410570053)

Identification of biomarkers for non-obstructive azoospermia based on microRNA and bioinformatics screening

Zhihong Li¹(), Miaoqi Chen¹(), Xiaojun Yuan¹, Huajun Huang¹, Wanting Huang¹, Piaoyan Zhou¹, Chen Zeng¹, Xunuo Feng¹, Luoyao Yang¹, Shuqiang Huang¹, Cuiyu Tan¹, Cairong Chen¹^,², Qiuxia Yan¹^,²()

1. Center for Reproductive Medicine, the Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan, 511518, China
2. Guangdong Engineering Technology Research Center of Urinary Continence and Reproductive Medicine, the Affiliated Qingyuan Hospital (Qingyuan People's Hospital), Guangzhou Medical University, Qingyuan 511518, China

Received:2025-07-02 Revised:2025-10-24 Published:2026-03-20 Online:2025-10-30
Supported by:
Guangdong Basic and Applied Basic Research Foundation(2025A1515012629);Guangdong Basic and Applied Basic Research Foundation(2023A1515220129);Guangdong Basic and Applied Basic Research Foundation(2019A1515010249);Scientific Research Project of Guangdong Province Bureau of Traditional Chinese Medicine(20241387);Open Research Funds from the Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University(202301-306);Open Research Funds from the Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University(202301-104);Plan on Enhancing Innovation Capacity in Guangzhou Medical University(240603131131);Plan on Enhancing Innovation Capacity in Guangzhou Medical University(240603131129);Innovation training Program for university students in Guangdong province(S202410570053)

摘要/Abstract

摘要：

microRNA (miRNA)在非梗阻性无精子症(non-obstructive azoospermia，NOA)的发生中发挥着重要作用，但目前仍缺乏对其调控靶基因表达介导NOA发生分子机制的研究。本研究从GEO数据库获取NOA相关的miRNA数据集，通过差异分析、加权基因共表达网络分析(weighted correlation network analysis，WGCNA)和LASSO回归筛选得到4个关键miRNA。基于miRDB数据库预测miRNA的靶点基因，与NOA转录组数据集的差异表达基因(differential expressed genes，DEGs)取交集，获得18个DEGs。精子发生评分模型显示18个DEGs总表达水平与精子发生评分呈显著正相关，证明上述DEGs可能与NOA的发生相关。将18个DEGs纳入机器学习，最终鉴定出4个最具有诊断价值的关键基因MGARP、FER1L5、SNX2和PAPOLB。在NOA小鼠模型中，MGARP与SNX2表达上调，而FER1L5与PAPOLB表达下调，与NOA数据集表达趋势一致。以上结果表明MGARP、FER1L5、SNX2和PAPOLB可作为NOA的新型标志物，为NOA的机制研究与临床诊断提供理论基础和实验依据。

关键词: miRNA, 非梗阻性无精子症, 精子发生, 机器学习, 生物信息学

Abstract:

MicroRNAs (miRNAs) play an important role in the occurrence of non-obstructive azoospermia (NOA). Nevertheless, there is still a lack of research on the molecular mechanisms by which miRNAs regulate target genes to mediate NOA at present. In this study, we obtained NOA-related miRNA datasets from the GEO database and applied differential expression matrices combined with weighted correlation network analysis (WGCNA) and LASSO regression to identify four key miRNAs. Based on the miRDB database, the target genes of these miRNAs were predicted and intersected with the differentially expressed genes (DEGs) in the NOA transcriptome datasets. This intersection resulted in the identification of 18 DEGs. The spermatogenesis score model revealed a significant positive correlation between the overall expression level of these 18 DEGs and spermatogenesis scores, suggesting their potential involvement in NOA development. These 18 DEGs were subsequently incorporated into machine learning, leading to the identification of four hub genes with high diagnostic value: MGARP, FER1L5, SNX2, and PAPOLB. In the NOA mouse model, MGARP and SNX2 were upregulated, whereas FER1L5 and PAPOLB were downregulated, consistent with the expression trends observed in the NOA datasets. These findings indicate that MGARP, FER1L5, SNX2, and PAPOLB may serve as novel biomarkers for NOA, providing a theoretical and experimental foundations for elucidating its mechanisms and improving clinical diagnosis.

Key words: miRNA, non-obstructive azoospermia, spermatogenesis, machine learning, bioinformatics

李志宏, 陈淼琪, 袁晓珺, 黄华君, 黄琬婷, 周飘雁, 曾晨, 冯许诺, 杨洛瑶, 黄树强, 谭翠钰, 陈彩蓉, 颜秋霞. 基于microRNA与生物信息学筛选非梗阻性无精子症的生物标志物[J]. 遗传, 2026, 48(3): 301-312.

Zhihong Li, Miaoqi Chen, Xiaojun Yuan, Huajun Huang, Wanting Huang, Piaoyan Zhou, Chen Zeng, Xunuo Feng, Luoyao Yang, Shuqiang Huang, Cuiyu Tan, Cairong Chen, Qiuxia Yan. Identification of biomarkers for non-obstructive azoospermia based on microRNA and bioinformatics screening[J]. Hereditas(Beijing), 2026, 48(3): 301-312.

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基于microRNA与生物信息学筛选非梗阻性无精子症的生物标志物

Identification of biomarkers for non-obstructive azoospermia based on microRNA and bioinformatics screening

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