Department of Human Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, 100026, China.
Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
J Ovarian Res. 2024 Sep 13;17(1):185. doi: 10.1186/s13048-024-01510-4.
In-depth understanding of dynamic expression profiles of human granulosa cells (GCs) during follicular development will contribute to the diagnostic and targeted interventions for female infertility. However, genome-scale analysis of long non-coding ribonucleic acid (lncRNA) in GCs across diverse developmental stages is challenging. Meanwhile, further research is needed to determine how aberrant lncRNA expression participates in ovarian diseases.
Granulosa cell-related lncRNAs data spanning five follicular development stages were retrieved and filtered from the NCBI dataset (GSE107746). Stage-specific lncRNA expression patterns and mRNA-lncRNA co-expression networks were identified with bioinformatic approaches. Subsequently, the expression pattern of SNHG18 was detected in GCs during ovarian aging. And SNHG18 siRNA or overexpression plasmids were transfected to SVOG cells in examining the regulatory roles of SNHG18 in GC proliferation and apoptosis. Moreover, whether PKCɛ/SNHG18 signaling take part in GC glycolysis via ENO1 were verified in SVOG cells.
We demonstrated that GC-related lncRNAs were specifically expressed across different developmental stages, and coordinated crucial biological functions like mitotic cell cycle and metabolic processes in the folliculogenesis. Thereafter, we noticed a strong correlation of PRKCE and SNHG18 expression in our analysis. With downregulated SNHG18 of GCs identified in the context of ovarian aging, SNHG18 knockdown could further induce cell apoptosis, retard cell proliferation and exacerbate DNA damage in SVOG cell. Moreover, downregulated PKCɛ/SNHG18 pathway interrupted the SVOG cell glycolysis by lowering the ENO1 expression.
Altogether, our results revealed that folliculogenesis-related lncRNA SNHG18 participated in the pathogenesis of ovarian aging, which may provide novel biomarkers for ovarian function and new insights for the infertility treatment.
深入了解人类卵泡期颗粒细胞（GCs）的动态表达谱将有助于女性不孕的诊断和靶向干预。然而，对不同发育阶段的 GC 中长链非编码核糖核酸（lncRNA）进行全基因组分析具有挑战性。同时，还需要进一步研究异常 lncRNA 表达如何参与卵巢疾病。
从 NCBI 数据集（GSE107746）中检索并筛选了跨越五个卵泡发育阶段的颗粒细胞相关 lncRNA 数据。采用生物信息学方法鉴定阶段特异性 lncRNA 表达模式和 mRNA-lncRNA 共表达网络。随后，在卵巢衰老过程中检测 SNHG18 在 GCs 中的表达模式。并用 SNHG18 siRNA 或过表达质粒转染 SVOG 细胞，研究 SNHG18 对 GC 增殖和凋亡的调控作用。此外，还在 SVOG 细胞中验证了 PKCɛ/SNHG18 信号是否通过 ENO1 参与 GC 糖酵解。
我们证明了 GC 相关的 lncRNA 是在不同的发育阶段特异性表达的，并协调了有丝分裂细胞周期和代谢过程等关键的生物学功能，参与了卵泡发生。此后，我们在分析中注意到 PRKCE 和 SNHG18 表达之间存在很强的相关性。在卵巢衰老的背景下，下调 GCs 中的 SNHG18 可以进一步诱导细胞凋亡，减缓 SVOG 细胞的增殖并加重 DNA 损伤。此外，下调 PKCɛ/SNHG18 通路通过降低 ENO1 的表达中断了 SVOG 细胞的糖酵解。
总之，我们的研究结果揭示了卵泡发生相关的 lncRNA SNHG18 参与了卵巢衰老的发病机制，这可能为卵巢功能提供新的生物标志物，并为不孕治疗提供新的见解。
