title: Silencing MARCH1 suppresses proliferation, migration and invasion of ovarian cancer SKOV3 cells via downregulation of NF-κB and Wnt/β-catenin pathways.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Tinghe
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, P.R. China.
authors.forename: Lina
authors.initials: L
authors.lastname: Hu
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D016328:NF-kappa B / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D051996:Transcription Factor RelA / Q000096:biosynthesis / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
chemical_list: D016328:NF-kappa B; C498143:RELA protein, human; D051996:Transcription Factor RelA; D051176:beta Catenin; C528121:MARCHF1 protein, human; D044767:Ubiquitin-Protein Ligases