RESUMEN
Background: Colorectal cancer (CRC) is a common malignant tumor in the digestive tract. Circular RNAs (circRNAs) have been identified as crucial regulators of tumorigenesis. However, the role and potential mechanism of circ_0004585 in CRC are poorly understood. Methods: The expression of circ_0004585, microRNA-338-3p (miR-338-3p), and zinc finger protein X-linked (ZFX) was detected by quantitative real-time PCR and Western blot. Cell proliferation, cell cycle arrest, apoptosis, and angiogenesis were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), 5-Ethynyl-2'-deoxyuridine (EdU), flow cytometry and tube formation assays. Western blot assay was applied to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins and MEK/ERK signaling pathway-related proteins. A xenograft model was used to analyze tumor growth in vivo. The targeted relationship between miR-338-3p and circ_0004585/ZFX was verified by a dual-luciferase reporter assay. Results: Circ_0004585 and ZFX were up-regulated, while miR-338-3p was down-regulated in CRC tissues and cells. Silencing of circ_0004585 inhibited proliferation, angiogenesis, and EMT and triggered apoptosis in CRC cells. Consistently, circ_0004585 depletion blocked tumor growth in vivo. Circ_0004585 contributed to CRC cell development via sequestering miR-338-3p. Also, miR-338-3p hindered the malignant progression of CRC cells by targeting ZFX. Circ_0004585 activated MEK/ERK pathway via regulating ZFX. Conclusion: Circ_0004585 facilitated CRC progression through modulating miR-338-3p/ZFX/MEK/ERK pathway, which might provide a potential therapeutic target for CRC. Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-022-00756-6.
RESUMEN
BACKGROUND: Circular RNAs (circRNAs) are essential participants in the development and progression of various malignant tumors. Previous studies have shown that cell migration-inducing protein (CEMIP) accelerates prostate cancer (PCa) anoikis resistance (AR) by activating autophagy. This study focused on the effect of circCEMIP on PCa metastasis. METHODS: This study gradually revealed the role of circ_0004585 in PCa anoikis resistance via quantitative real-time PCR (qRT-PCR) analysis, western blotting, pull-down assays, and dual fluorescence reporter assays. RESULTS: Functionally, circ_0004585 promoted PCa cells invasion and metastasis both in vitro and in vivo. Mechanistically, circ_0004585 directly interacted with miR-1248 to upregulate target gene expression. Furthermore, target prediction and dual-luciferase reporter assays identified transmembrane 9 superfamily member 4 (TM9SF4) as a potential miR-1248 target. Pathway analysis revealed that TM9SF4 activated autophagy to promote PCa cells anoikis resistance via mTOR phosphorylation. CONCLUSIONS: These results demonstrated that circ_0004585 played an oncogenic role during PCa invasion and metastasis by targeting the miR-1248/TM9SF4 axis while providing new insight into therapeutic strategy development for metastatic PCa.
