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

Circ_0006174通过miR-1205/CCBE1/Wnt通路促进结直肠癌细胞恶性化

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作者:Xun Zhao #, Dejun Cui #, Fang Yan, Liuchan Yang, Manman Zhang, Bo Huang

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/CCBE1/Wnt pathway.

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