ArticleMolecular therapy. Nucleic acids2018
MiR-663a Stimulates Proliferation and Suppresses Early Apoptosis of Human Spermatogonial Stem Cells by Targeting NFIX and Regulating Cell Cycle.
Article in Molecular therapy. Nucleic acids, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 39 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
- Pluripotency and cellular differentiation miRNAs expressed in human blastocoel fluid are associated with embryo quality.Journal of assisted reproduction and genetics · 2026Article
- 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
- Unraveling the Regulatory Function of MicroRNAs in Reproductive System Apoptosis and Their Implications for Infertility.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- Identification of biomarkers of male infertility through the circRNA expression profiling of seminal plasma.Journal of biomedical research · 2025Article
- Overgrowth-intellectual disability disorders: progress in biology, patient advocacy and innovative therapies.Disease models & mechanisms · 2025Review
- The microRNA-mediated apoptotic signaling axis in male reproduction: a possible and targetable culprit in male infertility.Cell biology and toxicology · 2025Review
- NFIX suppresses breast cancer cell proliferation by delaying mitosis through downregulation of CDK1 expression.Cell death discovery · 2025Article
- Combinational regenerative inductive effect of bio-adhesive hybrid hydrogels conjugated with hiPSC-derived myofibers and its derived EVs for volumetric muscle regeneration.Bioactive materials · 2025Article
- Small RNAs, spermatogenesis, and male infertility: a decade of retrospect.Reproductive biology and endocrinology : RB&E · 2023Review
- Current Progress in Stem Cell Therapy for Male Infertility.Stem cell reviews and reports · 2023Review
- NFIXing Cancer: The Role of NFIX in Oxidative Stress Response and Cell Fate.International journal of molecular sciences · 2023Review
- Alpha-tocopherol enhances spermatogonial stem cell proliferation and restores mouse spermatogenesis by up-regulating BMI1.Frontiers in nutrition · 2023Article
- SPOC domain-containing protein 1 regulates the proliferation and apoptosis of human spermatogonial stem cells through adenylate kinase 4.World journal of stem cells · 2022Article
- Regulation of mammalian spermatogenesis by miRNAs.Seminars in cell & developmental biology · 2022Review
- Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosome Repairs Endometrial Epithelial Cells Injury Induced by Hypoxia via Regulating miR-663a/CDKN2A Axis.Oxidative medicine and cellular longevity · 2022Article
- Integrated bioinformatics analysis of the transcription factor-mediated gene regulatory networks in the formation of spermatogonial stem cells.Frontiers in physiology · 2022Article
- Current scenario and challenges ahead in application of spermatogonial stem cell technology in livestock.Journal of assisted reproduction and genetics · 2021Review
- MicroRNA-30a-5p promotes differentiation in neonatal mouse spermatogonial stem cells (SSCs).Reproductive biology and endocrinology : RB&E · 2021Article
- Epigenetic Regulation of Spermatogonial Stem Cell Homeostasis: From DNA Methylation to Histone Modification.Stem cell reviews and reports · 2021Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human spermatogonial stem cells (SSCs) could have significant applications in reproductive medicine and regenerative medicine because of their great plasticity. The fate determinations of human SSCs are mediated by epigenetic factors. However, nothing is known about the regulation of non-coding RNA on human SSCs. Here we have explored for the first time the expression, function, and target of miR-663a in human SSCs. MiR-663a was upregulated in human spermatogonia compared with pachytene spermatocytes, as indicated by microRNA microarray and real-time PCR. CCK-8 and 5-Ethynyl-2'-deoxyuridine (EDU) assays revealed that miR-663a stimulated cell proliferation and DNA synthesis of human SSCs. Annexin V and propidium iodide (PI) staining and flow cytometry demonstrated that miR-663a inhibited early and late apoptosis of human SSCs. Furthermore, NFIX was predicted and verified as a direct target of miR-663a. NFIX silencing led to an enhancement of cell proliferation and DNA synthesis and a reduction of the early apoptosis of human SSCs. NFIX silencing neutralized the influence of miR-663a inhibitor on the proliferation and apoptosis of human SSCs. Finally, both miR-663a mimics and NFIX silencing upregulated the levels of cell cycle regulators, including Cyclin A2, Cyclin B1, and Cyclin E1, whereas miR-663a inhibitor had an adverse effect. Knockdown of Cyclin A2, Cyclin B1, and Cyclin E1 led to the decrease in the proliferation of human SSCs. Collectively, miR-663a has been identified as the first microRNA that promotes the proliferation and DNA synthesis and suppresses the early apoptosis of human SSCs by targeting NFIX via cell cycle regulators Cyclin A2, Cyclin B1, and Cyclin E1. This study thus provides novel insights into the molecular mechanisms underlying human spermatogenesis, and it could offer novel targets for treating male infertility and other human diseases.
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Registered trials
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