Exosomal circCOL1A2 from cancer cells accelerates colorectal cancer progression via regulating miR-665/LASP1 signal axis

Zhi Miao; Xiaomeng Zhao; Xiang Liu

doi:10.1016/j.ejphar.2023.175722

Exosomal circCOL1A2 from cancer cells accelerates colorectal cancer progression via regulating miR-665/LASP1 signal axis

Eur J Pharmacol. 2023 Jul 5:950:175722. doi: 10.1016/j.ejphar.2023.175722. Epub 2023 Apr 12.

Authors

Zhi Miao¹, Xiaomeng Zhao², Xiang Liu³

Affiliations

¹ Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China. Electronic address: 1019207167@tju.edu.cn.
² Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, 300072, China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.
³ Department of Laboratory Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, China; The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China.

PMID: 37059374
DOI: 10.1016/j.ejphar.2023.175722

Abstract

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.

Keywords: Colorectal cancer; LASP1; circCOL1A2; miR-665.

MeSH terms

Animals
Biological Assay
Carcinogenesis
Cell Line, Tumor
Cell Proliferation / genetics
Cell Transformation, Neoplastic
Colorectal Neoplasms* / genetics
MicroRNAs* / genetics

Substances

MicroRNAs