circPUM1 Promotes Tumorigenesis and Progression of Ovarian Cancer by Sponging miR-615-5p and miR-6753-5p
circPUM1 Promotes Tumorigenesis and Progression of Ovarian Cancer by Sponging miR-615-5p and miR-6753-5p
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circPUM1 通过海绵 miR-615-5p 和 miR-6753-5p 促进卵巢癌的肿瘤发生和进展
DOI：
10.1016/j.omtn.2019.09.032
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发表时间：
2019-12-06
影响因子：
8.8
通讯作者：
Zhao, Yang
中科院分区：
文献类型：
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作者：
Guan, Xue;Zong, Zhi-hong;Zhao, Yang
环状RNA（circRNA）参与了人类肿瘤的分子机制。目前已证实，卵巢癌的发生、发展与β 1基因密切相关。本研究旨在探讨circumstance 1在卵巢癌中的作用及其分子机制。qRT-PCR分析显示，与正常卵巢相比，卵巢癌组织中的circulatory 1上调。获得和丧失功能的实验表明，circumstance 1增加细胞增殖，迁移和侵袭，并抑制细胞凋亡。在裸鼠中腹膜内注射circumstance 1敲除的肿瘤细胞导致肿瘤的转移能力降低。生物信息学分析和双荧光素酶报告基因分析显示，circumstance 1通过海绵状作用于miR-615- 5 p和miR-6753- 5 p，上调核因子κ B（NF-κ B B）和MMP 2的表达。进一步的研究表明，外泌体circum 1作用于腹膜间皮细胞，增加肿瘤转移。综上所述，我们的研究表明，circumstance 1不仅促进卵巢癌的增殖，迁移和侵袭，而且还作用于腹膜，并以癌源性外泌体的形式促进癌症的转移。
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-kappa B) 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.