miRNA-103 通过调控 IRS1/PI3K/AKT 信号轴促进多囊卵巢综合征的进展。
microRNA-103 Contributes to Progression of Polycystic Ovary Syndrome Through Modulating the IRS1/PI3K/AKT Signal Axis.
机构信息
Department of Endocrinology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, P.R. China; Department of Endocrinology, Shenzhen SAMII Medical Center, Shenzhen 518118, Guangdong, P.R. China.
Department of Endocrinology, Shenzhen SAMII Medical Center, Shenzhen 518118, Guangdong, P.R. China.
出版信息
Arch Med Res. 2021 Jul;52(5):494-504. doi: 10.1016/j.arcmed.2021.01.008. Epub 2021 Feb 11.
BACKGROUND
Polycystic ovary syndrome (PCOS) is a frequent gynecological endocrine disorder, and the majority of PCOS patients experience different degrees of insulin resistance (IR). Nevertheless, the functions of microRNAs (miRNAs) in IR of PCOS remain unclear. In this study, we desired to elucidate the mechanisms of miR-103 in IR of PCOS.
METHODS
The ovarian pathological morphology of established PCOS rats was detected by HE staining. Following miR-103 expression determination in the ovarian tissues of PCOS rats, the relationship between its expression and IR was studied. A PCOS/IR cell model was established, and the effect of miR-103 on granulosa cells was determined by CCK-8 assay and flow cytometry. Through online website prediction and consulting related literatures, the target gene of miR-103 and the pathway regulated by the target genes were discovered, which was verified by further experiments.
RESULTS
PCOS rats showed polycystic changes in the ovary and a decrease in granulosa cells, and these symptoms were more pronounced in rats showed IR. miR-103 expressed highly in PCOS and was positively related to IR. miR-103 inhibitor led to improved PCOS-related symptoms. In addition, miR-103 directly targeted IRS1, which was poorly expressed in PCOS, and IRS1 silencing promoted PCOS development. Furthermore, miR-103 regulated the PI3K/AKT pathway by targeting IRS1, and PI3K/AKT pathway suppression reduced the therapeutic effect of miR-103 inhibitor.
CONCLUSION
This study indicates that miR-103 disrupts the PI3K/AKT pathway activation by targeting IRS1, thereby aggravating PCOS development. miR-103 inhibition may be a promising molecular target for treatment of PCOS.
背景
多囊卵巢综合征（PCOS）是一种常见的妇科内分泌疾病，大多数 PCOS 患者存在不同程度的胰岛素抵抗（IR）。然而，miRNAs（miRNA）在 PCOS 中 IR 的作用尚不清楚。在本研究中，我们旨在阐明 miR-103 在 PCOS 中 IR 的机制。
方法
通过 HE 染色检测已建立的 PCOS 大鼠的卵巢病理形态。检测 PCOS 大鼠卵巢组织中 miR-103 的表达后，研究其表达与 IR 的关系。建立 PCOS/IR 细胞模型，通过 CCK-8 检测和流式细胞术测定 miR-103 对颗粒细胞的影响。通过在线网站预测和查阅相关文献，发现 miR-103 的靶基因及其调控的通路，并通过进一步的实验进行验证。
结果
PCOS 大鼠的卵巢出现多囊性改变，颗粒细胞减少，IR 大鼠的这些症状更为明显。miR-103 在 PCOS 中表达较高，与 IR 呈正相关。miR-103 抑制剂可改善 PCOS 相关症状。此外，miR-103 直接靶向 IRS1，而 IRS1 在 PCOS 中表达较差，IRS1 沉默促进了 PCOS 的发展。此外，miR-103 通过靶向 IRS1 调控 PI3K/AKT 通路，PI3K/AKT 通路抑制降低了 miR-103 抑制剂的治疗效果。
结论
本研究表明，miR-103 通过靶向 IRS1 破坏 PI3K/AKT 通路的激活，从而加重 PCOS 的发展。抑制 miR-103 可能是治疗 PCOS 的有前途的分子靶点。
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