circRAE1 promotes colorectal cancer cell migration and invasion by modulating miR-338-3p/TYRO3 axis

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.

Circular RNA CNOT2 knockdown regulates twist family BHLH transcription factor via targeting microRNA 409-3p to prevent breast cancer invasion, migration and epithelial–mesenchymal transition

“…The cell migration was detected as set forth [ 13 ]. Transwell chamber (Corning, U.S.) was applied in this assay.…”

Molecular interactions of miR-338 during tumor progression and metastasis

“…There was an increased level of cir-cRAE1 in CRC tissues that was correlated with advanced TNM stage, tumor size, and lymph node involvement. It also promoted colorectal tumor cell migration by miR-388-3p sponging to upregulate TYRO3 [32]. RAB14 is an oncogenic GTPase involved in cell proliferation and invasion through regulation of the AKT pathway [33,34].…”

The roles and mechanisms of the circular RNA circ_104640 in early-stage lung adenocarcinoma: a potential diagnostic and therapeutic target

“…Due to the unique circular closed structure, high stability, and special expression patterns, it is believed that circRNAs can become potential biomarkers (25). In fact, circRNAs are dysregulated in various cancers, including LUACs (26)(27)(28). Several studies have suggested that dysregulated circRNAs in tissues or plasma could be used as novel biomarkers for cancer (29,30).…”