马拉特1
多囊卵巢
基因敲除
下调和上调
竞争性内源性RNA
生物
癌症研究
信号转导
转化生长因子
长非编码RNA
细胞生物学
内分泌学
内科学
细胞凋亡
医学
基因
遗传学
胰岛素抵抗
胰岛素
作者
Dan Zhang,Hong-Yuan Tang,Li Tan,Dongmei Zhao
标识
DOI:10.1016/j.mce.2019.110589
摘要
Polycystic ovary syndrome (PCOS) is an endocrine disorder, the etiology of which is complex and unclear. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a conserved long non-coding RNA which has been found to play a role in the pathophysiological process of reproductive system diseases, such as endometriosis and pregnancy loss. However, the role of MALAT1 in PCOS is still unknown. In this study, reduced MALAT1 expression was found in granulosa cells (GCs) from 68 patients with PCOS and 30 healthy controls, which relates to upregulated cell proliferation and downregulated apoptosis. Using phosphorylation pathway profiling array, MALAT1 reduction was identified to contribute to the repression of transforming growth factor beta (TGFβ) signaling in GCs. Subsequently, MALAT1 was confirmed to function as a competing endogenous RNA (ceRNA), interacting with miR-125b and miR-203a. Meanwhile, miR-125b and miR-203a was identified as two novel TGFβ signaling negative regulators by targeting TGFBR1 and TGFBR2. Finally, MALAT1 knockdown was found to induce the upregulation of miR-125b and miR-203a, which further repressed TGFβ signaling, changed some downstream gene expression, and resulted in a disordered cell cycle. In conclusion, MALAT1 reduction was identified in GCs, which may contribute to the pathophysiological processes of PCOS by regulating TGFβ signaling through sponging miR-125b and miR-203a.
科研通智能强力驱动
Strongly Powered by AbleSci AI