circRAE1 promotes colorectal cancer cell migration and invasion by modulating miR-338-3p/TYRO3 axis
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Cancer Cell International Open Access
PRIMARY RESEARCH
circRAE1 promotes colorectal cancer cell migration and invasion by modulating miR‑338‑3p/TYRO3 axis Jiabin Du, Jianhua Xu†, Junxing Chen, Weinan Liu, Pengcheng Wang and Kai Ye*
Abstract Background: Growing evidence has revealed the involvement of circular RNAs (circRNAs) in numerous carcinogenesis. However, the role of circRNAs in the cancer biology of colorectal cancer (CRC) remains vague. Methods: Quantitative RT-PCR was used to detect the expression level of circRAE1 in CRC tissues and CRC cell lines. Cell proliferation, migration, and invasion were detected using CCK8 assay, Colony formation assay, wound-healing and Transwell assays. The interaction between circRAE1 and miR-338-3p and TRYO3 was confirmed using dual-luciferase reporter assays. Results: We uncovered a novel circRNA Hsa_circ_0060967 (also known as circRAE1) that was remarkably increased in CRC tissues. The high circRAE1 level was positively associated with advanced tumor stage, lymph node metastasis, and tumor size. The loss-of-function assay showed that circRAE1 accelerated cell proliferation, migration, and invasion. Besides, miR-338-3p was lowly expressed in the CRC tissues and CRC cell lines. The dual-luciferase reporter assays showed that circRAE1 could sponge miR-338-3p, which targeted TRYO3 in CRC cells. Furthermore, the overexpression of circRAE1 could rescue the impaired migration and invasion triggered by miR-338-3p mimics or si-TYRO3 in CRC cells and vice versa. Conclusion: We identified the network of circRAE1, miR-338-3p, and TYRO3 in CRC cells and determined that the increase in circRAE1 could serve as an oncogene by sponging miR-338-3p, which resulted in an upregulated TYRO3 expression. The finding suggests that circRAE1 is a potential therapeutic target and diagnostic marker for CRC treatment. Keywords: circRNAs, Colorectal cancer, circRAE1, miR-338-3p, TYRO3 Background Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide, leading to more than 600,000 deaths each year [1, 2]. Approximately 25% of patients with CRC were reported to have distant metastasis at the time of diagnosis. In addition, 25% of the *Correspondence: [email protected] † Jianhua Xu—Co-first author Department of Gastrointestinal Surgery, Second Affiliated Hospital of Fujian Medical University, No.950 Donghai Dajie, Fengze District, Quanzhou 362000, Fujian, China
patients experienced metastasis during treatment, and the prognosis of advanced patients was poor, with a 5-year survival rate for less than 15% of them [1]. With the advances in the diagnosis and treatment of CRCs, the 5-year relative survival rates of patients with stage I or II disease have increased to 91% and 82%, respectively [3]. However, the 5-year survival rate decreased to 12% among patients suffering distant metastasis [3]. Therefore, further clinical research is needed to improve the 5-year survival rate of CRC patients with distant metastasis as a means of enhancing treatment efficiency, and the molecula
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