Knockdown of circ_0006528 Suppresses Cell Proliferation, Migration, Invasion, and Adriamycin Chemoresistance via Regulating the miR-1236-3p/CHD4 Axis in Breast Cancer.

BACKGROUND

Adriamycin (ADM) is one of the postoperative chemotherapy drugs for breast cancer (BCa) patients. Circular RNAs have been shown to modulate ADM resistance in many cancers. However, it is unclear whether circ_0006528 can modulate the ADM chemoresistance in BCa.

METHODS

Levels of circ_0006528, microRNA-1236-3p (miR-1236-3p), and chromodomain helicase DNA-binding protein 4 (CHD4) were detected by quantitative real-time polymerase chain reaction or western blot. Cell proliferation, the half maximal inhibitory concentration (IC50) value of ADM, and cell migration and invasion were evaluated by cell counting kit-8 and transwell assays, respectively. The interaction among circ_0006528, miR-1236-3p, and CHD4 was confirmed using dual-luciferase reporter assays. Tumor formation in nude mice was performed to explore the effect of circ_0006528 in vivo.

RESULTS

Higher levels of circ_0006528 and CHD4 and lower level of miR-1236-3p were found in ADM-resistant BCa tissues and cells, and patients with high circ_0006528 had a shorter overall survival. Circ_0006528 could directly bind to miR-1236-3p, and circ_0006528 knockdown or miR-1236-3p overexpression could suppress cell proliferation, migration, invasion, and ADM resistance in ADM-resistant BCa cells. Moreover, circ_0006528-regulated CHD4 expression by sponging miR-1236-3p, and CHD4 elevation reversed the inhibitory effect of circ_0006528 knockdown on ADM-resistant BCa cells. Consistently, circ_0006528 inhibition retarded ADM-resistant BCa tumor growth in vivo by decreasing CHD4 and increasing miR-1236-3p.

CONCLUSIONS

Downregulation of circ_0006528 restrained cell proliferation, migration, invasion, and drug resistance of ADM-resistant BCa cells through inhibiting CHD4 and inducing miR-1236-3p.