Department of Gynaecology, The Third Xiangya Hospital of Central South University, Changsha, China.
J Cell Mol Med. 2020 Jan;24(1):451-464. doi: 10.1111/jcmm.14753. Epub 2019 Nov 16.
It has been found that long noncoding RNA HOTAIR, microRNA-130a (miR-130a) and insulin-like growth factor 1 (IGF1) expression are associated with ovarian cancer, thus, we hypothesised that the HOTAIR/miR-130a/IGF1 axis might associate with endocrine disorders and biological behaviours of ovarian granulosa cells in rat models of polycystic ovary syndrome (PCOS). PCOS rat models were established by injection of dehydro-isoandrosterone, followed by treatment of si-HOTAIR, oe-HOTAIR, miR-130a mimics or miR-130a inhibitors. Serum hormonal levels were determined to evaluate endocrine conditions. The effect of HOTAIR and miR-130a on activities of isolated ovarian granulosa cells was assessed, as well as the involvement of IGF1.In the ovarian tissues and granulosa cells of PCOS rat models, highly expressed HOTAIR and IGF1 and poorly expressed miR-130a were identified. In response to oe-HOTAIR, serum levels of E , T and LH were increased and serum levels of FSH were reduced; the proliferation of granulosa cells was reduced and apoptosis was promoted; notably, expression of miR-130a was reduced while expression of IGF1 was increased. The treatment of si-HOTAIR reversed the situation. Furthermore, the binding of HOTAIR to miR-130a and targeting relationship of miR-130a and IGF1 were confirmed. LncRNA HOTAIR up-regulates the expression of IGF1 and aggravates the endocrine disorders and granulosa cell apoptosis through competitive binding to miR-130a in rat models of PCOS. Based on our finding, we predict that competitive binding of HOTAIR to miR-130a may act as a novel target for the molecular treatment of PCOS.
现已发现长链非编码 RNA HOTAIR、微小 RNA-130a（miR-130a）和胰岛素样生长因子 1（IGF1）的表达与卵巢癌有关，因此，我们假设 HOTAIR/miR-130a/IGF1 轴可能与多囊卵巢综合征（PCOS）大鼠模型中的卵巢颗粒细胞内分泌紊乱和生物学行为有关。通过注射脱氢异雄酮建立 PCOS 大鼠模型，然后用 si-HOTAIR、oe-HOTAIR、miR-130a 模拟物或 miR-130a 抑制剂进行处理。测定血清激素水平以评估内分泌状况。评估 HOTAIR 和 miR-130a 对分离的卵巢颗粒细胞活性的影响，以及 IGF1 的参与。在 PCOS 大鼠模型的卵巢组织和颗粒细胞中，发现 HOTAIR 和 IGF1 高表达，miR-130a 低表达。oe-HOTAIR 作用后，E、T 和 LH 血清水平升高，FSH 血清水平降低；颗粒细胞增殖减少，凋亡增加；miR-130a 表达减少，IGF1 表达增加。si-HOTAIR 的处理逆转了这种情况。此外，还证实了 HOTAIR 与 miR-130a 的结合以及 miR-130a 与 IGF1 的靶向关系。LncRNA HOTAIR 通过与 miR-130a 竞争结合，上调 IGF1 的表达，加重 PCOS 大鼠模型的内分泌紊乱和颗粒细胞凋亡。基于我们的发现，我们预测 HOTAIR 与 miR-130a 的竞争结合可能成为 PCOS 分子治疗的新靶点。
