Guan Xue, Zong Zhi-Hong, Liu Yao, Chen Shuo, Wang Li-Li, Zhao Yang
Department of Gynecology, the First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang 110013, China.
Mol Ther Nucleic Acids. 2019 Dec 6;18:882-892. doi: 10.1016/j.omtn.2019.09.032. Epub 2019 Oct 23.
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.
据报道，环状RNA（circRNAs）参与人类癌症的分子机制。PUM1基因已被证实与卵巢癌的发生和进展密切相关。在本研究中，我们探讨了circPUM1在卵巢癌中的功能及潜在分子机制。qRT-PCR分析显示，与正常卵巢相比，circPUM1在卵巢癌组织中表达上调。功能获得和缺失实验表明，circPUM1促进细胞增殖、迁移和侵袭，并抑制细胞凋亡。在裸鼠腹腔注射circPUM1敲除的肿瘤细胞导致肿瘤转移能力下降。生物信息学分析和双荧光素酶报告基因检测显示，circPUM1通过海绵吸附miR-615-5p和miR-6753-5p上调核因子κB（NF-κB）和MMP2的表达。进一步研究表明，外泌体circPUM1作用于腹膜间皮细胞并增加肿瘤转移。总之，我们的研究表明，circPUM1不仅促进卵巢癌的增殖、迁移和侵袭，还作用于腹膜，并以癌源性外泌体的形式促进癌症转移。
