College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China.
Anhui Provincial Key Laboratory of Livestock and Poultry Product Safety Engineering, Institute of Animal Husbandry and Veterinary Medicine, Anhui Academy of Agricultural Sciences, Hefei 230031, China.
Cells. 2024 Sep 19;13(18):1571. doi: 10.3390/cells13181571.
Circular RNAs (circRNAs) are a class of circular non-coding RNAs that play essential roles in the intricate and dynamic networks governing cell growth, development, and apoptosis. Resveratrol (RSV), a non-flavonoid polyphenol, is known to participate in follicular development and ovulation. In our previous research, we established a model using porcine ovarian granulosa cells (POGCs) treated with resveratrol, which confirmed its regulatory effects on long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) within these cells. However, the influence of resveratrol on circRNA expression has not been thoroughly investigated. To explore how resveratrol affects circRNA levels in POGCs, we designed an experiment with three groups: a control group (CON, n = 3, 0 μM RSV), a low-dose RSV group (LOW, n = 3, 50 μM RSV), and a high-dose RSV group (HIGH, n = 3, 100 μM RSV) for circRNA sequencing. We identified a total of 10,045 candidate circRNAs from POGCs treated with different concentrations of resveratrol (0, 50, and 100 μM). Differential expression analysis indicated that 96 circRNAs were significantly altered in the LOW vs. CON group, while 109 circRNAs showed significant changes in the HIGH vs. CON group. These circRNAs were notably enriched in biological processes associated with cell metabolism, apoptosis, and oxidative stress. Functional enrichment analysis of the host genes revealed their involvement in critical signaling pathways, including mTOR, AMPK, and apoptosis pathways. Additionally, we identified potential miRNA sponge candidates among the differentially expressed circRNAs, particularly novel_circ_0012954 and novel_circ_0004762, which exhibited strong connectivity within miRNA-target networks. Our findings provide valuable insights into the regulatory mechanisms of circRNAs in the context of resveratrol-induced apoptosis in POGCs, highlighting their potential as innovative therapeutic targets in reproductive biology.
环状 RNA（circRNA）是一类环状非编码 RNA，在调控细胞生长、发育和凋亡的复杂动态网络中发挥重要作用。白藜芦醇（RSV）是一种非黄酮多酚，已知参与卵泡发育和排卵。在我们之前的研究中，我们使用经过白藜芦醇处理的猪卵巢颗粒细胞（POGC）建立了一个模型，证实了它对这些细胞内长链非编码 RNA（lncRNA）和 microRNA（miRNA）的调节作用。然而，白藜芦醇对 circRNA 表达的影响尚未得到深入研究。为了探讨白藜芦醇如何影响 POGC 中的 circRNA 水平，我们设计了一个实验，分为三组：对照组（CON，n = 3，0 μM RSV）、低剂量 RSV 组（LOW，n = 3，50 μM RSV）和高剂量 RSV 组（HIGH，n = 3，100 μM RSV）进行 circRNA 测序。我们从不同浓度白藜芦醇（0、50 和 100 μM）处理的 POGC 中鉴定出总共 10045 个候选 circRNA。差异表达分析表明，LOW 与 CON 组相比，有 96 个 circRNA 显著改变，而 HIGH 与 CON 组相比，有 109 个 circRNA 显著改变。这些 circRNA 显著富集在与细胞代谢、凋亡和氧化应激相关的生物学过程中。宿主基因的功能富集分析表明，它们参与了关键的信号通路，包括 mTOR、AMPK 和凋亡通路。此外，我们在差异表达的 circRNA 中鉴定出了潜在的 miRNA 海绵候选物，特别是 novel_circ_0012954 和 novel_circ_0004762，它们在 miRNA-靶网络中表现出很强的连接性。我们的研究结果为白藜芦醇诱导 POGC 凋亡过程中 circRNA 的调控机制提供了有价值的见解，强调了它们作为生殖生物学中创新治疗靶点的潜力。
