Circ_0006174 promotes the malignancy of colorectal cancer cell via the miR-1205/CCBE1/Wnt pathway

Abstract

Circular RNAs (circRNAs) are novel RNA transcripts that participate in cancer development. Nonetheless, in colorectal cancer (CRC), the information ~circRNA expression and function is largely unknown. The present study aimed to investigate the expression, function and underlying mechanism of circ_0006174 in CRC. Reverse transcription-quantitative PCR analysis was performed to detect circ_0006174, miR-1205 and calcium-binding epidermal growth factor domain-containing protein 1 (CCBE1) expression levels in CRC tissues and cell lines. Circ_0006174 knockdown CRC cell models were established. CCK-8, TUNEL and Transwell methods were utilized to explore the function of circ_0006174 on the malignant phenotype of CRC cells. Moreover, a xenograft nude mouse model was constructed to verify the effects of circ_0006174 on lung metastasis in vivo. Dual-luciferase reporter gene assay was adopted to prove the association between circ_0006174 and miR-1205, miR-1205 and CCBE1. Gene set enrichment analysis was performed using the LinkedOmics database. Western blotting was performed to evaluate the expression of CCBE1, Ki67 and Wnt pathway-related proteins (c-Myc and cyclin D1) in CRC cell lines. Circ_0006174 showed a notable upregulation in CRC tissues and cell lines and its overexpression was linked to larger tumor diameter and advanced T stage of CRC patients. Circ_0006174 knockdown significantly suppressed cell growth and metastatic potential and promoted cell apoptosis in vitro. Circ_0006174 knockdown accelerated the lung metastasis in vivo. Mechanistically, circ_0006174 could decoy miR-1205 to up-modulate CCBE1 expression and Wnt pathway.related proteins (c.Myc and cyclin D1). Circ_0006174 is an oncogenic circRNA , which participates in the promotion of CRC progression by regulating the miR-1205/CC BE1/Wnt pathway.