circPUM1 Promotes Tumorigenesis and Progression of Ovarian Cancer by Sponging miR-615-5p and miR-6753-5p

• Published in: Molecular therapy. Nucleic acids Vol. 18; pp. 882 - 892
• Main Authors: Guan, Xue, Zong, Zhi-hong, Liu, Yao, Chen, Shuo, Wang, Li-li, Zhao, Yang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.12.2019; Elsevier Limited; American Society of Gene & Cell Therapy; Elsevier
• Subjects: Apoptosis; Binding sites; Bioinformatics; Cell adhesion & migration; Cell growth; Cell migration; Cell proliferation; circRNA; exosome; Exosomes; Experiments; Gelatinase A; Gene expression; Metastases; Metastasis; microRNA; MicroRNAs; Morphology; NF-κB protein; Ovarian cancer; Peritoneum; Plasmids; progression; Proteins; Tumor cells; Tumorigenesis; United States > US; China; microRNA; progression; tumorigenesis; circRNA; ovarian cancer; exosome
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2019.09.032

Circular RNAs (circRNAs) have been reported to participate in the molecular mechanism of human cancers. The PUM1 gene has been confirmed to be closely related to tumorigenesis and progression of ovarian cancer. In the present study, we explored the function and underlying molecular mechanism of circPUM1 in ovarian cancer. qRT-PCR analysis showed upregulation of circPUM1 in ovarian cancer tissues compared with normal ovaries. Gain- and loss-of-function experiments indicated that circPUM1 increased cell proliferation, migration, and invasion and inhibited cell apoptosis. Intraperitoneal injection of circPUM1-knockout tumor cells in nude mice resulted in a decrease in the metastatic ability of the tumor. Bioinformatics analysis and dual-luciferase reporter assays revealed that circPUM1 upregulated the expression of nuclear factor kappa B (NF-κB) and MMP2 by sponging miR-615-5p and miR-6753-5p. Further studies showed that exosomal circPUM1 acted on peritoneal mesothelial cells and increased tumor metastasis. In conclusion, our study indicates that circPUM1 not only promotes ovarian cancer proliferation, migration and invasion, but also acts on the peritoneum and contributes to metastasis of cancer in the form of cancer-derived exosomes. [Display omitted]