CircFBXW4 Suppresses Colorectal Cancer Progression by Regulating the MiR‐338‐5p/SLC5A7 Axis

• DOI: 10.1002/advs.202300129
• Publication Date: 2024-03-10T15:24:56Z
• Authors: Wei Song; Jincheng Fu; Jing Wu; Jun Ren; Rensheng Xiang; Can Kong; Tao Fu
• Keywords: Male; Monocarboxylic Acid Transporters; 0303 health sciences; Science; Q; Mice, Nude; colorectal cancer; RNA, Circular; circFBXW4; SLC5A7; miR‐338‐5p; Gene Expression Regulation, Neoplastic; MicroRNAs; Mice; Disease Models, Animal; 03 medical and health sciences; Cell Line, Tumor; Disease Progression; Humans; Animals; Female; Colorectal Neoplasms; Research Articles; Cell Proliferation

AbstractDysregulated circular RNAs (circRNAs) contribute to tumourigenesis and cancer progression. However, the expression patterns and biological functions of circRNAs in colorectal cancer (CRC) remain elusive. Here, RNA sequencing and bioinformatics analyses are applied to screen for aberrantly expressed circRNAs. The expression of circFBXW4 in CRC tissues and cell lines is determined by quantitative real‐time PCR. A series of in vitro and in vivo biological function assays are implemented to assess the functions of circFBXW4. The regulatory mechanisms linking circFBXW4, miR‐338‐5p, and SLC5A7 are explored by western blotting, dual luciferase reporter assays, and RNA pull‐down assays. CircFBXW4 is dramatically downregulated in CRC tissues and cell lines. circFBXW4 downregulation is clearly correlated with malignant features and patient overall survival in CRC. Functionally, ectopic expression of circFBXW4 strikingly impairs the proliferation, migration, and invasion capacities of CRC cells in vitro and in vivo, whereas circFBXW4 knockdown has the opposite effects. Mechanistically, circFBXW4 competitively binds to miR‐338‐5p and prevents it from interacting with and repressing its target SLC5A7, thus suppressing the progression of CRC. This study reveals the specific critical role of circFBXW4 in inhibiting CRC progression via the miR‐338‐5p/SLC5A7 axis and provides an additional target for eradicating CRC.