Interaction of E3 Ubiquitin Ligase MARCH7 with Long Noncoding RNA MALAT1 and Autophagy-Related Protein ATG7 Promotes Autophagy and Invasion in Ovarian Cancer

• Main Authors: Jianguo Hu, Luo Zhang, Zhiqiang Mei, Yuan Jiang, Yuan Yi, Li Liu, Ying Meng, Lili Zhou, Jianhua Zeng, Huan Wu, Xingwei Jiang
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2018-05-01
• Series: Cellular Physiology and Biochemistry
• Subjects: March7; MALAT1; ATG7; Autophagy; Smad2/3; Ovarian cancer; Invasion
• Online Access: https://www.karger.com/Article/FullText/490020
• ISSN: 1015-8987; 1421-9778

Background/Aims: Ubiquitin E3 ligase MARCH7 plays an important role in T cell proliferation and neuronal development. But its role in ovarian cancer remains unclear. This study aimed to investigate the role of Ubiquitin E3 ligase MARCH7 in ovarian cancer. Methods: Real-time PCR, immunohistochemistry and western blotting analysis were performed to determine the expression of MARCH7, MALAT1 and ATG7 in ovarian cancer cell lines and clinical specimens. The role of MARCH7 in maintaining ovarian cancer malignant phenotype was examined by Wound healing assay, Matrigel invasion assays and Mouse orthotopic xenograft model. Luciferase reporter assay, western blot analysis and ChIP assay were used to determine whether MARCH7 activates TGF-β-smad2/3 pathway by interacting with TGFβR2. Results: MARCH7 interacted with MALAT1 by miR-200a (microRNA-200a). MARCH7 may function as a competing endogenous RNA (ceRNA) to regulate the expression of ATG7 by competing with miR-200a. MARCH7 regulated TGF-β-smad2/3 pathway by interacting with TGFβR2. Inhibition of TGF-β-smad2/3 pathway downregulated MARCH7, MALAT1 and ATG7. MiR-200a regulated TGF-β induced autophagy, invasion and metastasis of SKOV3 cells by targeting MARCH7. MARCH7 silencing inhibited autophagy invasion and metastasis of SKOV3 cells both in vitro and in vivo. In contrast, MARCH7 overexpression promoted TGF-β induced autophagy, invasion and metastasis of A2780 cells in vitro by depending on MALAT1 and ATG7. We also found that TGF-β-smad2/3 pathway regulated MARCH7 and ATG7 through MALAT1. Conclusions: These findings suggested that TGFβR2-Smad2/3-MALAT1/MARCH7/ATG7 feedback loop mediated autophagy, migration and invasion in ovarian cancer.