CircRBM33 facilitates colorectal cancer progression by regulating the miR-512-5p/SLC1A5 axis

Colorectal cancer (CRC) is a common malignant tumor of the digestive tract with high morbidity and mortality. Previous studies have shown that circular RNA (circRNA) circRBM33 (also known as hsa_circRNA_104532) was implicated in the pathogenesis of various human cancers. This study aims to investigate the potential function and working mechanism of circRBM33 in CRC.

circRBM33, microRNA-512-5p (miR-512-5p), and solute carrier 1 family member 5 (SLC1A5) levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferative ability, apoptosis, and migration were analyzed using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, and wound healing assay. C-myc, CyclinD1, and SLC1A5 protein levels were measured using Western blot. The glycolysis levels were evaluated using specific kits. The biological role of circRBM33 on CRC tumor growth was assessed using the xenograft tumor model in vivo. After circular RNA Interactome and Targetscan prediction, the binding between miR-512-5p and circRBM33 or SLC1A5 was verified using a dual-luciferase reporter assay.

CircRBM33 and SLC1A5 were increased, and miR-512-5p was decreased in CRC tissues and cells. From a functional perspective, circRBM33 knockdown could hinder cell proliferation, migration, glutamine metabolism, and boost apoptosis in CRC cells. Also, circRBM33 silencing could suppress the cell growth of CRC in vivo. The mechanical analysis suggested that circRBM33 could increase SLC1A5 expression via sponging miR-512-5p.

CircRBM33 boosted CRC development partly by regulating the miR-512-5p/SLC1A5 axis, providing a promising therapeutic target for CRC therapy.