4.6 Article

CircCDR1 sponges miR-1290 to regulate cell proliferation, migration, invasion, and apoptosis in esophageal squamous cell cancer

期刊

CELL CYCLE
卷 21, 期 12, 页码 1316-1334

出版社

TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2022.2050645

关键词

ESCC; circCDR1; miR-1290; xenotransplant tumor; growth

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In this study, it was found that circCDR1 regulates the progression of esophageal squamous cell cancer (ESCC) by acting as a sponge for miR-1290. CircCDR1 is low-expressed and negatively correlated with miR-1290 in ESCC. In both in vitro and in vivo experiments, circCDR1 inhibits proliferation, migration, and invasion of ESCC cells, while promoting apoptosis.
Since circCDR1 was abnormally expressed in esophageal squamous cell cancer (ESCC), the current study explored whether circCDR1 affected ESCC. Detailedly, circCDR1 expression in ESCC and linear isoform and stability of circCDR1 were detected by RT-qPCR. The location of circCDR1 was detected by fluorescence in situ hybridization (FISH). After transfection, the cell biological functions were detected by wound-healing, CCK-8, colony formation, and flow cytometry assays. The target of circCDR1 was predicted by bioinformatics, FISH, RNA pull-down, and dual-luciferase reporter assays. The correlation between circCDR1 and miR-1290 was analyzed by Pearson's correlation analysis. A subcutaneous-xenotransplant tumor model in BALB/c nude mice was established and the levels of circCDR1, miR-1290, and apoptosis/metastasis/proliferation-related factors in the cancer cells and tissues were detected by immunohistochemical analysis, western blot, or RT-qPCR. As a result, circCDR1 was low-expressed in ESCC tissues and cells, while miR-1290 was high-expressed. CircCDR1 was regulated and was negatively correlated with miR-1290. CircCDR1, located in cytoplasm, inhibited the viability, proliferation, migration, and invasion of the cancer cells and the expressions of Bcl-2, N-cadherin, and Vimentin, but enhanced cell apoptosis and the expressions of C caspase-3, Bax, E-cadherin, IGFBP4, LHX6 and NFIX. In vivo, circCDR1 promoted xenotransplanted tumor weight and volume, and the expressions of C caspase-3 and Bax yet suppressed the levels of Bcl-2, miR-1290, and Ki-67 in tumor tissues. The effects of circCDR1 on both cancer cells and tissues were opposite to and reversed by miR-1290 mimic. Collectively, circCDR1 sponged miR-1290 to regulate the progression of ESCC both in vitro and in vivo.

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