期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 950, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2023.175722
关键词
Colorectal cancer; miR-665; LASP1
This study investigated the effect and mechanism of a novel circRNA (circCOL1A2) in colorectal cancer (CRC). The study found that circCOL1A2 was highly expressed in CRC cells and could be transferred via exosomes. Reduction of exosomal circCOL1A2 inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) properties. Mechanism studies demonstrated the binding of miR-665 with circCOL1A2 or LASP1. Animal studies confirmed the oncogenic function of exosomal circCOL1A2 in CRC tumorigenesis.
Circular RNAs (circRNAs) have been demonstrated to exert pivotal functions in cancer progression but are poorly understood in colorectal cancer (CRC). This work intends to investigate the effect and mechanism of a novel cirRNA (circCOL1A2) in CRC. Exosomes were identified via transmission electron microscope (TEM) and nanoparticle tracking analysis (NTA). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to analyze the levels of genes and proteins. Proliferation, migration, and invasion were detected via cell counting kit-8 (CCK8), 5-Ethynyl-2 '-deoxyuridine (EDU), and transwell experiments. RNA pull-down, luciferase reporter, and RNA immunoprecipitation (RIP) assays were performed to assess the binding between genes. Animal studies were carried out to evaluate the function of circCOL1A2 in vivo. We found that circCOL1A2 was highly expressed in CRC cells. And circCOL1A2 was packaged from cancerous cells into exosomes. The proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) properties were inhibited after the reduction of exosomal circCOL1A2. Mechanism studies proved the binding of miR-665 with circCOL1A2 or LASP1 Rescue experiments validated the reverse effects of miR-665 knockdown on circCOL1A2 silencing and LASP1 overexpression on miR-665. Animal studies further confirmed the oncogenic function of exosomal circCOL1A2 in CRC tumorigenesis. In conclusion, exosomal circCOL1A2 sponges miR-665 to enhance LASP1 expression and modulated CRC phenotypes. Thus, circCOL1A2 might be a valuable therapeutic target for CRC, offering novel insight into CRC treatment.
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