泛素化调控几乎涵盖所有细胞过程。泛素化信号的失调与多种疾病的发生和进展密切相关。然而，在精子发生和癌症中泛素化调控因子（UBRs）的相互作用和潜在功能方面缺乏综合性研究。我们系统性地表征了不同组织中UBRs的mRNA和蛋白质表达，并进一步评估了它们在睾丸发育和精子生成中的作用。随后，我们探讨了泛癌中UBRs的基因变异、表达紊乱、与癌症标志通路的关系以及临床相关性。这项工作揭示了UBRs在不同组织中的表达模式的异质性，其中睾丸中的表达模式最为独特。UBRs在睾丸发育过程中呈动态表达，对正常精子生成至关重要。此外，UBRs在泛癌中普遍存在基因变异和表达紊乱。我们确定了79个UBRs的表达与32个癌症标志通路的活性密切相关，并通过基于网络的方法筛选出十个核心基因进行进一步的临床相关性分析。超过90%的UBRs可以影响癌症患者的生存，并且核心基因对特定癌症类型具有良好的预后分类能力。我们的研究在精子生成和泛癌中对UBRs进行了全面分析，为理解男性不育和开发与泛素化相关的癌症药物奠定了基础。© 2023. BioMed Central Ltd., part of Springer Nature.

Ubiquitination controls almost all cellular processes. The dysregulation of ubiquitination signals is closely associated with the initiation and progression of multiple diseases. However, there is little comprehensive research on the interaction and potential function of ubiquitination regulators (UBRs) in spermatogenesis and cancer.We systematically characterized the mRNA and protein expression of UBRs across tissues and further evaluated their roles in testicular development and spermatogenesis. Subsequently, we explored the genetic alterations, expression perturbations, cancer hallmark-related pathways, and clinical relevance of UBRs in pan-cancer.This work reveals heterogeneity in the expression patterns of UBRs across tissues, and the expression pattern in testis is the most distinct. UBRs are dynamically expressed during testis development, which are critical for normal spermatogenesis. Furthermore, UBRs have widespread genetic alterations and expression perturbations in pan-cancer. The expression of 79 UBRs was identified to be closely correlated with the activity of 32 cancer hallmark-related pathways, and ten hub genes were screened for further clinical relevance analysis by a network-based method. More than 90% of UBRs can affect the survival of cancer patients, and hub genes have an excellent prognostic classification for specific cancer types.Our study provides a comprehensive analysis of UBRs in spermatogenesis and pan-cancer, which can build a foundation for understanding male infertility and developing cancer drugs in the aspect of ubiquitination.© 2023. BioMed Central Ltd., part of Springer Nature.