Chang Yue, Hao Min, Jia Ru, Zhao Yihui, Cai Yixuan, Liu Yun
Department of Obstetrics and Gynecology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing, China.
Cancer Cell Int. 2021 Jan 7;21(1):29. doi: 10.1186/s12935-020-01682-1.
Endometrial cancer is an invasive gynecological cancer prevalent in the world. The pathogenesis of endometrial cancer is related to multiple levels of regulation, referring to oestrogen, tumor-suppressor gene (e.g. PTEN) or microRNAs (e.g. miR-23a and miR-29b). Metapristone is a hormone-related drug, which is widely used in clinical treatment of endometrial cancer. However, the underlying regulatory mechanism of metapristone on endometrial cancer is still unclear, especially the regulatory effect on microRNAs. The aim of this study is to investigate the specific molecular mechanism of metapristone regulating microRNAs in the treatment of endometrial cancer.
RL95-2 cells and Ishikawa cells were used as the endometrial cancer models. MiR-492 or si-miR-492 was transfected into RL95-2 cells and Ishikawa cells to explore the role of miR-492 in endometrial cancer. The cell cancer model and mice cancer model were used to confirm the function and mechanism of metapristone affected on endometrial cancer in vitro and in vivo. Mechanically, cell proliferation was monitored using MTT assay, cell colony formation assay and EdU assay. Luciferase reporter assay was used to identify the downstream target gene of miR-492. The protein expression and RNA expression were respectively measured by western blot and qRT-PCR for cell signaling pathway research, subsequently, were verified in the mice tumor model via immunohistochemistry.
Metapristone as a kind of hormone-related drug significantly inhibited the endometrial cancer cell growth through regulating cell apoptosis-related gene expression. Mechanically, miR-492 and its target genes Klf5 and Nrf1 were highly expressed in the endometrial cancer cell lines, which promoted cell proliferation and inhibited cell apoptosis. Metapristone decreased the expression of miR-492 and its target genes Klf5 and Nrf1, leading to endometrial cancer cell growth inhibition in vitro and in vivo.
Metapristone inhibited the endometrial cancer cell growth through regulating the cell apoptosis-related signaling pathway and decreasing the expression of miR-492 and its downstream target genes (Klf5 and Nrf1), which provided the theoretical basis in clinical treatment of endometrial cancer.
子宫内膜癌是一种在全球范围内普遍存在的侵袭性妇科癌症。子宫内膜癌的发病机制与多个调控层面相关，涉及雌激素、肿瘤抑制基因（如PTEN）或微小RNA（如miR - 23a和miR - 29b）。甲地孕酮是一种与激素相关的药物，广泛应用于子宫内膜癌的临床治疗。然而，甲地孕酮对子宫内膜癌的潜在调控机制仍不清楚，尤其是对微小RNA的调控作用。本研究的目的是探讨甲地孕酮在子宫内膜癌治疗中调控微小RNA的具体分子机制。
以RL95 - 2细胞和Ishikawa细胞作为子宫内膜癌模型。将miR - 492或si - miR - 492转染到RL95 - 2细胞和Ishikawa细胞中，以探究miR - 492在子宫内膜癌中的作用。利用细胞癌模型和小鼠癌模型在体外和体内证实甲地孕酮对子宫内膜癌的作用及其机制。具体而言，使用MTT法、细胞集落形成试验和EdU试验监测细胞增殖。采用荧光素酶报告基因试验鉴定miR - 492的下游靶基因。分别通过蛋白质印迹法和qRT - PCR检测蛋白质表达和RNA表达，用于细胞信号通路研究，随后通过免疫组织化学在小鼠肿瘤模型中进行验证。
甲地孕酮作为一种与激素相关的药物，通过调节细胞凋亡相关基因的表达，显著抑制子宫内膜癌细胞的生长。具体机制为，miR - 492及其靶基因Klf5和Nrf1在子宫内膜癌细胞系中高表达，促进细胞增殖并抑制细胞凋亡。甲地孕酮降低了miR - 492及其靶基因Klf5和Nrf1的表达，导致体外和体内子宫内膜癌细胞生长受到抑制。
甲地孕酮通过调节细胞凋亡相关信号通路以及降低miR - 492及其下游靶基因（Klf5和Nrf1）的表达来抑制子宫内膜癌细胞的生长，为子宫内膜癌的临床治疗提供了理论依据。
