ArticleReproductive biology and endocrinology : RB&E2019
Downregulation of miR-322 promotes apoptosis of GC-2 cell by targeting Ddx3x.
Article in Reproductive biology and endocrinology : RB&E, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 29 citations in OpenAlex.
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- Unique miRomics Expression Profiles inInternational journal of molecular sciences · 2023Article
- Unraveling the harmful effect of oxidative stress on male fertility: A mechanistic insight.Frontiers in endocrinology · 2023Review
- Infertility in Men: Advances towards a Comprehensive and Integrative Strategy for Precision Theranostics.Cells · 2022Review
- Studying the mechanism of sperm DNA damage caused by folate deficiency.Journal of cellular and molecular medicine · 2022Article
- LncRNA MIR4435-2HG functions as a ceRNA against miR-125a-5p and promotes neuroglioma development by upregulating TAZ.Journal of clinical laboratory analysis · 2021Article
- Micronutrient imbalance and common phenotypes in neural tube defects.Genesis (New York, N.Y. : 2000) · 2021Review
- The effect of SiNPs on DNA methylation of genome in mouse spermatocytes.Environmental science and pollution research international · 2021Article
- PbAc Triggers Oxidation and Apoptosis via the PKA Pathway in NRK-52E Cells.Biological trace element research · 2021Article
- Megalocytivirus Induces Complicated Fish Immune Response at Multiple RNA Levels Involving mRNA, miRNA, and circRNA.International journal of molecular sciences · 2021Article
- The Vehicle Determines the Destination: The Significance of Seminal Plasma Factors for Male Fertility.International journal of molecular sciences · 2020Review
- Seminal Plasma Transcriptome and Proteome: Towards a Molecular Approach in the Diagnosis of Idiopathic Male Infertility.International journal of molecular sciences · 2020Review
- miR-322 treatment rescues cell apoptosis and neural tube defect formation through silencing NADPH oxidase 4.CNS neuroscience & therapeutics · 2020Article
- Abundant Neural circRNA Cdr1as Is Not Indispensable for Retina Maintenance.Frontiers in cell and developmental biology · 2020Article
- Advances in the diagnosis and treatment of oligoasthenozoospermia based on epigenetic regulation.Therapeutic advances in urologyReview
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAberrant DNA damage of germ cells, which impairs spermatogenesis and lowers fertility, is an important factor contributing to male infertility. MicroRNAs (miRNAs) play a significant role in the expression and regulation of multiple genes during spermatogenesis. Our previous study found much lower miR-424 (murine homologue miR-322) levels in the seminal plasma of infertile patients with high DFI(DNA Fragmentation Index)than in the fertile group. However, the mechanism by which miR-322 regulates germ cells during spermatogenesis remains unknown.
methodsIn this study, we successfully established a GC-2 cell model of miR-322 downregulation resulting in impaired spermatogenesis. And the cell viability were measured using Cell Counting Kit-8 (CCK-8; Dojindo, Japan) and MTT (Sigma Aldrich, USA). Immunofluorescence assay was used to detect cell damage and the expression of apoptosis-related proteins were measured using real-time quantitative PCR and Western blot analysis. Target genes were predicted and verified by online database retrieval and Dual-luciferase reporter gene assay.
resultsWe observed evident decreases in the cell viability of GC-2 cells along with remarkable increases in apoptosis after miR-322 inhibition. While the expression of apoptosis-related genes, including Bax and caspases 3, 9, and 8 greatly increased in GC-2 cells after miR-322 downregulation, that of the anti-apoptotic Bcl-2 gene decreased. Ddx3x was found to be the direct target of miR-322. MiR-424 was then detected in the seminal plasma of infertile patients with high DFI(DNA Fragmentation Index); this miRNA was down-regulated but Ddx3x was upregulated in the infertile group.
conclusionMiR-322 plays a key role in promoting GC-2 cell apoptosis by directly regulating Ddx3x expression. MiR-424 downregulation in infertile men may induce spermatogenic cell apoptosis and sperm DNA damage by directly acting on the target gene locus Ddx3x, resulting in male infertility.
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