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

• Published in: British journal of cancer Vol. 130; no. 9; pp. 1517 - 1528
• Main Authors: Deng, Li-Qiang, Shi, Chuan-Jian, Zhou, Shu-Ting, Zeng, Wei-Qiang, Xian, Yan-Fang, Wang, Yu-Yan, Fu, Wei-Ming, Lin, Han-Li, Liu, Wei, Zhang, Jin-Fang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.05.2024
• Subjects: 631/67/1857; 631/67/395; Biomedical and Life Sciences; Biomedicine; Cancer Research; Drug Resistance; Epidemiology; Molecular Medicine; Oncology
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/s41416-024-02612-y

Background 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. Methods 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. Results 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. Conclusions Our findings illustrated a novel mechanism of circβ-catenin in modulating CRC tumorigenesis and metastasis, which provides a potential therapeutic target for CRC patients.