Identification of circ_0058357 as a regulator in non-small cell lung cancer cells resistant to cisplatin by miR-361-3p/ABCC1 axis.

BACKGROUND

Drug resistance is a major clinical drawback behind the failure of chemotherapy in non-small cell lung cancer (NSCLC). In this study, we undertook to identify the precise role of circular RNA (circRNA) circ_0058357 in the functional properties of DDP-resistant NSCLC cells.

METHODS

Circ_0058357, miR-361-3p and ATP-binding cassette (ABC) subfamily C member 1 (ABCC1) were quantified by qRT-PCR and western blot. Cell survival and viability were gauged by MTT assay. Cell proliferation, apoptosis, invasion and migration were measured by EdU, flow cytometry, transwell and wound-healing assays, respectively. The direct relationship between miR-361-3p and circ_0058357 or ABCC1 was validated by dual-luciferase reporter assay.

RESULTS

Our data showed that circ_0058357 was highly expressed in DDP-resistant NSCLC tissues and cells. Inhibition of circ_0058357 repressed cell growth, invasion, migration, and promoted DDP sensitivity and cell apoptosis of H1299/DDP and A549/DDP cells in vitro. Moreover, inhibition of circ_0058357 diminished the growth of A549/DDP cells and sensitized them to the cytotoxic effect of DDP in vivo. Mechanistically, circ_0058357 contained a miR-361-3p binding site and miR-361-3p was identified as a molecular mediator of circ_0058357 regulation. MiR-361-3p suppressed ABCC1 expression by binding to ABCC1 3'UTR, and miR-361-3p-mediated inhibition of ABCC1 affected the growth, invasion, migration, apoptosis and DDP sensitivity of H1299/DDP and A549/DDP cells. Furthermore, circ_0058357 regulated ABCC1 expression by competitively binding to shared miR-361-3p.

CONCLUSIONS

Our findings identified that inhibition of circ_0058357 suppresses the growth and metastasis of H1299/DDP and A549/DDP cells and sensitizes them to DDP therapy partially by targeting the miR-361-3p/ABCC1 axis.