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EIF4A3-negatively driven circular RNA β-catenin (circβ-catenin) promotes colorectal cancer progression via miR-197-3p/CTNND1 regulatory axis

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机构: [1]Cancer center, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518000, China. [2]School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China. [3]Research Institute, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518000, China. [4]Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. [5]School of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China
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Circβ-catenin, our first reported circRNA, has been reported to mediate tumorigenesis in various cancers. However, its biological functions and underlying mechanisms in colorectal cancer (CRC) remain unknown.The qRT-PCR examination was used to detect the expression of circβ-catenin, miR-197-3p, and CTNND1 in cells and human tissues. Western blot was conducted to detect the protein expression levels. The biological function of circβ-catenin was verified by MTT, colony formation, wound healing, and transwell assays. The in vivo effects of circβ-catenin were verified by nude mice xenograft and metastasis models. The regulatory network of circβ-catenin/miR-197-3p/CTNND1 was confirmed via dual-luciferase reporter and RIP assays.In the present study, circβ-catenin was found to promote CRC cell proliferation and metastasis in vitro and in vivo. Mechanistically, circβ-catenin served as miRNA decoy to directly bind to miR-197-3p, then antagonized the repression of the target gene CTNND1, and eventually promoted the malignant phenotype of CRC. More interestingly, the inverted repeated Alu pairs termed AluJb1/2 and AluY facilitated the biogenesis of circβ-catenin, which could be partially reversed by EIF4A3 binding to Alu element AluJb2.Our findings illustrated a novel mechanism of circβ-catenin in modulating CRC tumorigenesis and metastasis, which provides a potential therapeutic target for CRC patients.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.

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大类 | 1 区 医学
小类 | 2 区 肿瘤学
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大类 | 2 区 医学
小类 | 2 区 肿瘤学
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Q1 ONCOLOGY
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Q1 ONCOLOGY

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第一作者机构: [1]Cancer center, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518000, China. [2]School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China. [3]Research Institute, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518000, China.
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通讯机构: [1]Cancer center, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518000, China. [3]Research Institute, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518000, China. [4]Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
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