circ_0038718 promotes colon cancer cell malignant progression via the miR-195-5p/Axin2 signaling axis and also effect Wnt/β-catenin signal pathway

被引:27
作者
Gu, Haitao [1 ]
Xu, Zhiquan [1 ]
Zhang, Jianbo [1 ]
Wei, Yanbing [2 ]
Cheng, Ling [2 ]
Wang, Jijian [1 ]
机构
[1] Chongqing Med Univ, Dept Gastrointestinal Surg, Affiliated Hosp 2, 288 Tianwen Dadao Rd, Chongqing 401336, Peoples R China
[2] Shanghai Engn Res Ctr Pharmaceut Translat, Shanghai 200231, Peoples R China
关键词
colon cancer; circ_0038718; Wnt; beta-catenin signaling pathway; Proliferation; Migration; Invasion; PROLIFERATION; OVEREXPRESSION; METASTASIS; COMPLEXITY; EXPRESSION; MIGRATION;
D O I
10.1186/s12864-021-07880-z
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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/beta-catenin signaling pathway. Oligo (dT) (18) 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/beta-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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页数:17
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