Circ_0038718 Promotes Colon Cancer Cell Malignant Progression Via the MiR-195-5p/Axin2 Signaling Axis and Also Effect Wnt/β-catenin Signal Pathway
Overview
Affiliations
Objective: Colon cancer (CC) is one of the most common cancers whose progression is regulated by a number of factors, including circular RNAs (circRNAs). Nonetheless, circ_0038718 is a novel circRNA, and its regulatory mechanism in CC remains unclear.
Methods: Real-time quantitative PCR (qRT-PCR) was performed to detect the expression of circ_0038718, miR-195-5p and Axin2. Western blot was conducted to determine the protein expression of Axin2 and the key proteins on Wnt/β-catenin signaling pathway. Oligo (dT) primers and RNase R were employed to identify the circular features of circ_0038718, and the location of circ_0038718 in cells was detected via nucleocytoplasmic separation. Dual-luciferase reporter assay and RNA binding protein immunoprecipitation experiment were carried out to investigate the molecular mechanism of circ_0038718/miR-195-5p/Axin2. Additionally, MTT assay was conducted to assess cell proliferation; Transwell assay was performed to evaluate cell migration and invasion, respectively. The effect of circ_0038718 on CC tumor growth was tested through tumor formation in nude mice.
Results: circ_0038718 was highly expressed in CC and could sponge miR-195-5p in cytoplasm. Silencing circ_0038718 suppressed the proliferative, migratory and invasive abilities of CC cells, while the promoting effect of high circ_0038718 expression on CC cells was reversed upon miR-195-5p over-expression. Axin2 was a downstream target of miR-195-5p and could regulate the Wnt/β-catenin signaling pathway. Axin2 expression was modulated by circ_0038718/miR-195-5p. Knockdown of Axin2 could also attenuate the promoting effect of high circ_0038718 expression on CC cell malignant progression, thus inhibiting tumor growth.
Conclusion: circ_0038718 is able to facilitate CC cell malignant progression via the miR-195-5p/Axin2 axis, which will provide a new idea for finding a novel targeted treatment of CC.
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Ou Z, Lu Y, Xu D, Luo Z Front Immunol. 2023; 14:1271603.
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Ge H, Yan Y, Wang H, Bian J, Deng Z, Su X Comb Chem High Throughput Screen. 2023; 28(1):99-109.
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Wang B, Shen W, Yan L, Li X, Zhang L, Zhao S Ann Med. 2023; 55(2):2244515.
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