ArticleBiological research2023
Ubiquitin protein E3 ligase ASB9 suppresses proliferation and promotes apoptosis in human spermatogonial stem cell line by inducing HIF1AN degradation.
Article in Biological research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 19 citations in OpenAlex.
- Molecular mechanisms and translational implications in apoptosis, ferroptosis, pyroptosis, and cuproptosis of spermatogonial stem cells.Cellular and molecular life sciences : CMLS · 2026Review
- Male germ cell-specific deletion ofZoological research · 2026Article
- The Mechanism of Histone Ubiquitylation by the ASB9-CUL5 Ubiquitin Ligase.Molecular & cellular proteomics : MCP · 2026Article
- Article
- RNF187 Facilitates Proliferation and Migration of Human Spermatogonial Stem Cells Through WDR77 Polyubiquitination.Cell proliferation · 2025Article
- The transcriptional regulation of NUPR1 expression by MYC is implicated in the regulation of ferroptosis in human spermatogonial stem cells.Cellular and molecular life sciences : CMLS · 2025Article
- Novel anoikis-related genes for the diagnosis of non-obstructive azoospermia.Translational andrology and urology · 2025Article
- RGS14 binds to GNAI3 and regulates the proliferation and apoptosis of human spermatogonial stem cells by affecting PLPP2 expression and MAPK signaling.Frontiers in cell and developmental biology · 2025Article
- CITED2 Binding to EP300 Regulates Human Spermatogonial Stem Cell Proliferation and Survival Through HSPA6.Stem cells international · 2025Article
- Essential Regulation of Spermatogonial Stem Cell Fate Decisions and Male Fertility by APBB1 via Interaction with KAT5 and GDF15 in Humans and Mice.Research (Washington, D.C.) · 2025Article
- PTN from Leydig cells activates SDC2 and modulates human spermatogonial stem cell proliferation and survival via GFRA1.Biological research · 2024Article
- EEF1B2 regulates the proliferation and apoptosis of human spermatogonial stem cell lines through TAF4B.Heliyon · 2024Article
- Review
- GPx3 knockdown inhibits the proliferation and DNA synthesis and enhances the early apoptosis of human spermatogonial stem cells via mediating CXCL10 and cyclin B1.Frontiers in cell and developmental biology · 2023Article
- MAGEB2-Mediated Degradation of EGR1 Regulates the Proliferation and Apoptosis of Human Spermatogonial Stem Cell Lines.Stem cells international · 2023Article
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5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundSpermatogonial stem cells (SSCs) are critical for sustaining spermatogenesis. Even though several regulators of SSC have been identified in rodents, the regulatory mechanism of SSC in humans has yet to be discovered.
methodsTo explore the regulatory mechanisms of human SSCs, we analyzed publicly available human testicular single-cell sequencing data and found that Ankyrin repeat and SOCS box protein 9 (ASB9) is highly expressed in SSCs. We examined the expression localization of ASB9 using immunohistochemistry and overexpressed ASB9 in human SSC lines to explore its role in SSC proliferation and apoptosis. Meanwhile, we used immunoprecipitation to find the target protein of ASB9 and verified its functions. In addition, we examined the changes in the distribution of ASB9 in non-obstructive azoospermia (NOA) patients using Western blot and immunofluorescence.
resultsThe results of uniform manifold approximation and projection (UMAP) clustering and pseudotime analysis showed that ASB9 was highly expressed in SSCs, and its expression gradually increased during development. The immunohistochemical and dual-color immunofluorescence results displayed that ASB9 was mainly expressed in nonproliferating SSCs. Overexpression of ASB9 in the SSC line revealed significant inhibition of cell proliferation and increased apoptosis. We predicted the target proteins of ASB9 and verified that hypoxia-inducible factor 1-alpha inhibitor (HIF1AN), but not creatine kinase B-type (CKB), has a direct interaction with ASB9 in human SSC line using protein immunoprecipitation experiments. Subsequently, we re-expressed HIF1AN in ASB9 overexpressing cells and found that HIF1AN reversed the proliferative and apoptotic changes induced by ASB9 overexpression. In addition, we found that ABS9 was significantly downregulated in some NOA patients, implying a correlation between ASB9 dysregulation and impaired spermatogenesis.
conclusionASB9 is predominantly expressed in human SSCs, it affects the proliferation and apoptotic process of the SSC line through HIF1AN, and its abnormal expression may be associated with NOA.
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