Department of Gynaecology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Cell Cycle. 2020 Mar;19(6):697-710. doi: 10.1080/15384101.2020.1724601. Epub 2020 Feb 23.
There is growing evidence of the position of microRNAs (miRs) in polycystic ovarian syndrome (PCOS), thus our objective was to discuss the impact of miR-204 on insulin resistance (IR) in PCOS by targeting highmobility group box protein 1(HMGB1)-mediated toll-like receptor 4(TLR4)/nuclear factor-kappa B (NF-κB) pathway.PCOS-IR patients and PCOS non-insulin resistance (PCOS-NIR) patients were included. The levels of serum sex hormones and related insulin were measured, the expression of miR-204, HMGB1, TLR4 and NF-κB p65 was detected, the diagnostic efficacy of miR-204 in PCOS-IR was analyzed, and the correlation between the expression of miR-204 in PCOS-IR and fasting blood glucose (FPG), fasting insulin (FINS), homeostasis model of assessment for insulin resistance index (HOMA-IR) was analyzed. Both and experiments were performed to elucidate the capabilities of miR-204 and HMGB1 in proliferation and apoptosis of PCOS-IR granulosa cells.MiR-204 was lowly expressed as well as HMGB1, TLR4 and NF-κB p65 were highly expressed in PCOS-IR patients. Follicule-stimulating hormone was downregulated, while luteinizing hormone, estrogen, progesterone, FPG, FINS and HOMA-IR were elevated in PCOS-IR. Upregulation of miR-204 and downregulation of HMGB1 could repress TLR4/NF-κB pathway activation, degraded insulin release and testosterone (T) leveland ascended ovarian coefficient, boosted cell proliferation and restrained apoptosis of granulosa cells. Overexpression of HMGB1 reverses the effect of upregulation of miR-204 on IR of PCOS.Our study presents that high expression of miR-204 or inhibition of HMGB1 can improve IR of PCOS via the inactivation of TLR4/NF-κB pathway.
多囊卵巢综合征（PCOS）中 microRNAs（miRs）的作用日益得到证实，因此我们的目的是通过靶向高迁移率族蛋白 B1（HMGB1）-介导的 Toll 样受体 4（TLR4）/核因子-κB（NF-κB）通路探讨 miR-204 对 PCOS 胰岛素抵抗（IR）的影响。纳入 PCOS-IR 患者和 PCOS 非胰岛素抵抗（PCOS-NIR）患者。测定血清性激素及相关胰岛素水平，检测 miR-204、HMGB1、TLR4 和 NF-κB p65 的表达，分析 miR-204 在 PCOS-IR 中的诊断效能，并分析 miR-204 在 PCOS-IR 中的表达与空腹血糖（FPG）、空腹胰岛素（FINS）、胰岛素抵抗指数评估的稳态模型（HOMA-IR）的相关性。进行 和 实验以阐明 miR-204 和 HMGB1 在 PCOS-IR 颗粒细胞增殖和凋亡中的作用。PCOS-IR 患者 miR-204 低表达，HMGB1、TLR4 和 NF-κB p65 高表达。促卵泡激素下调，而黄体生成素、雌激素、孕酮、FPG、FINS 和 HOMA-IR 升高。上调 miR-204 和下调 HMGB1 可抑制 TLR4/NF-κB 通路激活，降解胰岛素释放和睾酮（T）水平，升高卵巢系数，促进颗粒细胞增殖，抑制凋亡。HMGB1 的过表达逆转了 miR-204 对 PCOS IR 的上调作用。我们的研究表明，高表达 miR-204 或抑制 HMGB1 可以通过 TLR4/NF-κB 通路的失活来改善 PCOS 的 IR。
