Overexpression of miR-144-3p alleviates polycystic ovaries syndrome through targeting expression of HSP-70
Overexpression of miR-144-3p alleviates polycystic ovaries syndrome through targeting expression of HSP-70
复制标题
miR-144-3p 的过表达通过靶向 HSP-70 的表达缓解多囊卵巢综合征
DOI：
10.1038/s41434-020-00191-0
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发表时间：
2020-09-11
期刊：
影响因子：
5.1
通讯作者：
Zhang, Yan
中科院分区：
文献类型：
--
作者：
Qu, Bing;Zhao, Qinghong;Zhang, Yan
microRNAs的增加参与了多囊卵巢综合征（PCOS）的发病机制。然而，miR-144- 3 p的生物学效应及其在PCOS中的详细机制有待研究。本研究旨在探讨miR-144- 3 p在PCOS中的作用。目前，miR-144- 3 p在PCOS患者和PCOS大鼠模型中的表达显著降低。此外，HSP-70的表达也明显升高。在PCOS大鼠模型卵巢颗粒细胞中过表达miR-144- 3 p后，进行细胞增殖测定和流式细胞术测定。我们观察到miR-144- 3 p过表达诱导细胞增殖并抑制细胞凋亡，而miR-144- 3 p缺失则表现出相反的过程。将PCOS大鼠模型分为4组：LV-NC组、LV-miR-144- 3 p组、Anti-control组和Anti-miR-144- 3 p组。作为对miR-144- 3 p缺失的响应，我们发现E2、T和LH血清水平升高，FSH血清水平受到抑制。miR-144- 3 p的上调表现出相反的过程。此外，HSP-70是miR-144- 3 p的直接靶点。此外，HSP-70的表达增加挽救了miR-144- 3 p对卵巢颗粒细胞生长和凋亡的影响。此外，HSP-70的敲低减轻了体内内分泌紊乱和卵巢重量异常。综上所述，miR-144- 3 p可能通过靶向HSP-70而成为PCOS治疗的新靶点。
Increasing microRNAs are shown to be participate in polycystic ovarian syndrome (PCOS) pathogenesis. Nevertheless, the biological effects of miR-144-3p and its detailed mechanisms in PCOS are to be investigated. The purpose of our work was to study the function of miR-144-3p in PCOS. Currently, Expression of miR-144-3p was greatly reduced in PCOS patients and PCOS rat models. In addition, HSP-70 expression was greatly elevated PCOS. Cell proliferation assays and flow cytometry assay were carried out following the overexpression of miR-144-3p in ovarian granulosa cells from PCOS rat models. We observed that miR-144-3p overexpression induced the proliferation and repressed cell apoptosis while loss of miR-144-3p demonstrated an opposite process. Then, PCOS rat models were classified to four groups: LV-NC group, LV-miR-144-3p group, Anti-control group, and Anti-miR-144-3p group. In response to loss of miR-144-3p, we found E2, T, and LH serum levels were elevated and FSH serum level was inhibited. Upregulation of miR-144-3p exhibited an opposite process. Moreover, HSP-70 was a direct target of miR-144-3p. Furthermore, increased expression of HSP-70 rescued the effects of miR-144-3p on ovarian granulosa cell growth and apoptosis. In addition, knockdown of HSP-70 alleviated endocrine disorders and abnormal ovarian weight in vivo. To sum up, miR-144-3p might function as a novel target for PCOS treatment via targeting HSP-70.