Chen Xi, Xie Mingxuan, Liu Da, Shi Ke
Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Mol Med Rep. 2015 Oct;12(4):5155-62. doi: 10.3892/mmr.2015.4036. Epub 2015 Jul 3.
Premature ovarian failure (POF), an ovarian disorder of multifactorial origin, is defined as the occurrence of amenorrhea, hypergonadotropism and hypoestrogenism in females <40 years old. Apoptosis of ovarian granulosa cells is important in POF and understanding the regulatory mechanism underlying ovarian granulosa cell apoptosis may be beneficial for the management of POF. Increasing evidence suggests that microRNAs (miRs) have a regulatory function in oocyte maturation and ovarian follicular development. In the present study, the expression of miR‑146a in plasma and ovarian granulosa cells obtained from patients with POF, its effect on the apoptosis of ovarian granulosa cells and the possible underlying mechanisms were examined. The present study demonstrated that compared with the control groups, the expression of miR‑146a in the plasma and in ovarian granulosa cells of patients with POF was significantly upregulated. Furthermore, it was found that miR‑146a simultaneously targeted interleukin‑1 receptor‑associated kinase (IRAK1) and tumor necrosis factor receptor‑associated factor 6 (TRAF6), which regulated the activity of nuclear factor‑κB and IκBα. In addition, the results demonstrated that inhibition of the caspase cascade by caspase inhibitors attenuated the effects of miR‑146a on ovarian granulosa cell apoptosis. Taken together, these results suggest that miR‑146a has an important promoting effect on the apoptosis of granulosa cells by targeting IRAK1 and TRAF6 via the caspase cascade pathway. These results may be useful for the management of POF.
卵巢早衰（POF）是一种多因素起源的卵巢疾病，定义为40岁以下女性出现闭经、高促性腺激素血症和低雌激素血症。卵巢颗粒细胞凋亡在POF中起重要作用，了解卵巢颗粒细胞凋亡的调控机制可能有助于POF的治疗。越来越多的证据表明，微小RNA（miR）在卵母细胞成熟和卵泡发育中具有调节功能。在本研究中，检测了POF患者血浆和卵巢颗粒细胞中miR-146a的表达、其对卵巢颗粒细胞凋亡的影响以及可能的潜在机制。本研究表明，与对照组相比，POF患者血浆和卵巢颗粒细胞中miR-146a的表达显著上调。此外，发现miR-146a同时靶向白细胞介素-1受体相关激酶（IRAK1）和肿瘤坏死因子受体相关因子6（TRAF6），它们调节核因子-κB和IκBα的活性。此外，结果表明，半胱天冬酶抑制剂抑制半胱天冬酶级联反应可减弱miR-146a对卵巢颗粒细胞凋亡的影响。综上所述，这些结果表明，miR-146a通过半胱天冬酶级联途径靶向IRAK1和TRAF6，对颗粒细胞凋亡具有重要的促进作用。这些结果可能有助于POF的治疗。
