Circ_0000395 promotes cell growth, metastasis and oxaliplatin resistance by regulating miR-153-5p/MYO6 in colorectal cancer.

ABSTRACT

BACKGROUND: Circular RNAs (circRNAs) are involved in the regulation of colorectal cancer (CRC) progression and chemoresistence. Here, we attempted to reveal the function and mechanism of circ_0000395 in CRC chemoresistence. METHODS: The expression levels of circ_0000395, microRNA (miR)-153-5p, and myosin VI (MYO6) were determined by quantitative real-time PCR. Cell growth, metastasis and oxaliplatin resistance were evaluated via EdU assay, colony formation assay, flow cytometry, transwell assay, and cell counting kit 8 assay. Xenograft tumor model was adopted to evaluate the role of circ_0000395 on CRC tumor growth and oxaliplatin sensitivity. Protein expression of drug-resistance markers and MYO6 was analyzed by western blot. The target relationship between miR-153-5p and circ_0000395 or MYO6 was validated via dual-luciferase reporter assay and RIP assay. RESULTS: Circ_0000395 expression was enhanced in CRC tissues and cells. Silencing of circ_0000395 repressed CRC cell proliferation, migration and invasion, while promoted apoptosis and oxaliplatin sensitivity. Besides, circ_0000395 knockdown also reduced CRC tumor growth and enhanced the sensitivity of tumor to oxaliplatin. Additionally, circ_0000395 acted as a sponge for miR-153-5p, and miR-153-5p targeted MYO6. Functional experiments suggested that miR-153-5p inhibitor or MYO6 overexpression could reverse the suppressive effect of circ_0000395 knockdown on CRC cell growth, metastasis and oxaliplatin resistance. CONCLUSION: Circ_0000395 promoted CRC cell growth, metastasis and oxaliplatin resistance via the miR-153-5p/MYO6 axis, which might provide new insights into the treatment of CRC.