Meng Ying, Hu Jianguo, Chen Yuhong, Yu Tinghe, Hu Lina
Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China.
Oncol Rep. 2016 Nov;36(5):2463-2470. doi: 10.3892/or.2016.5076. Epub 2016 Sep 8.
Membrane-associated RING-CH (MARCH) belongs to the family of RING-CH type E3 ubiquitin ligases. MARCH1 ubiquitinates and downregulates MHC class II expression in APCs and targets major players of the immune system. However, the role of MARCH1 in ovarian cancer has not been elucidated. The present study investigated the function of MARCH1 in ovarian cancer and the potential mechanisms involved. MARCH1 expression was examined in human ovarian cancer tissue specimens by immunohistochemistry. The role of MARCH1 in ovarian cancer cells was assessed by cell proliferation, migration and invasion assays with MARCH1 gene silencing. To investigate the mechanism by which MARCH1 functions, correlation between MARCH1 and the cell signaling pathways were analyzed using a luciferase reporter assay, real-time RT-PCR, western blot assay and immunofluorescence. MARCH1 was found to be overexpressed in ovarian cancer tissues when compared to adjacent non-tumor and normal ovarian tissues. Silencing MARCH1 inhibited SKOV3 cell proliferation, invasion and migration, as well as inhibiting the NF-κB and the Wnt/β‑catenin pathways. MARCH1 functions as a tumor promoter by upregulating the NF-κB and the Wnt/β-catenin pathways, indicating that MARCH1 may be a therapeutic target for patients with ovarian cancer.
膜相关RING-CH(MARCH)属于RING-CH型E3泛素连接酶家族。MARCH1使抗原呈递细胞(APC)中的MHC II类分子泛素化并下调其表达,且作用于免疫系统的主要参与者。然而,MARCH1在卵巢癌中的作用尚未阐明。本研究调查了MARCH1在卵巢癌中的功能及相关潜在机制。通过免疫组织化学检测人卵巢癌组织标本中MARCH1的表达。采用MARCH1基因沉默的细胞增殖、迁移和侵袭实验评估MARCH1在卵巢癌细胞中的作用。为研究MARCH1发挥作用的机制,使用荧光素酶报告基因检测、实时逆转录聚合酶链反应(RT-PCR)、蛋白质免疫印迹法和免疫荧光分析MARCH1与细胞信号通路之间的相关性。结果发现,与相邻的非肿瘤卵巢组织和正常卵巢组织相比,MARCH1在卵巢癌组织中过表达。沉默MARCH1可抑制SKOV3细胞的增殖、侵袭和迁移,同时抑制核因子κB(NF-κB)和Wnt/β-连环蛋白信号通路。MARCH1通过上调NF-κB和Wnt/β-连环蛋白信号通路发挥肿瘤促进作用,表明MARCH1可能是卵巢癌患者的一个治疗靶点。