Circ_0000395 Promoted CRC Progression via Elevating MYH9 Expression by Sequestering miR-432-5p

Abstract

Colorectal cancer (CRC) has been listed as the fourth deadly cancer. Circular RNA hsa_circRNA_001046, also termed as hsa_circ_0000395 (circ_0000395), has been shown to be upregulated in CRC. Nevertheless, the function of circ_0000395 in CRC progression is unclear. 42 CRC patients were enrolled in the study. Detection of circ_0000395 expression in tissues and cells was executed using real-time quantitative polymerase chain reaction (RT-qPCR). Evaluation of circ_0000395 function was performed using loss-of-function experiments in vitro and in vivo. The regulatory mechanism of circ_0000395 was predicted by bioinformatics analysis and validated by dual-luciferase reporter and RIP assays. Exosomes were isolated by ultracentrifugation and validated by western blotting, TEM, and NTA. Circ_0000395 was strongly expressed in CRC samples and cell lines. Also, circ_0000395 repressed CRC growth in mouse models in vivo and induced CRC cell apoptosis, restrained CRC cell proliferation, migration, invasion, and EMT in vitro. Mechanistically, circ_0000395 sequestered miR-432-5p to regulate MYH9 expression. Furthermore, miR-432-5p knockdown reversed circ_0000395 silencing-mediated effects on CRC cell malignant phenotypes. MYH9 overexpression counteracted the inhibiting effects of miR-432-5p upregulation on CRC cell malignant phenotypes. Additionally, CRC cells derived from exosomal circ_0000395 promoted cancer cell malignant phenotypes. Our findings demonstrated that circ_0000395 sequestered miR-432-5p to elevate MYH9 expression, resulting in facilitating CRC progression, manifesting a potential therapeutic target for CRC.

Keywords: Colorectal cancer; Exosomes; MYH9; circ_0000395; miR-432-5p.