CircRNA_0044556 diminishes the sensitivity of triple-negative breast cancer cells to adriamycin by sponging miR-145 and regulating NRAS

CircRNAs are associated with adriamycin (ADM) resistance in triple-negative breast cancer (TNBC), but the mechanism is unknown. Reverse transcription-quantitative PCR was applied to quantify circular RNA (circRNA)_0044556, microRNA (miR)-145 and NRAS proto-oncogene, GTPase (NRAS) in TNBC tissues and cells with or without ADM treatment. Following ADM treatment, the effects of circRNA_0044556 on the viability, ADM resistance, apoptosis and migration of TNBC cells were investigated by cell function experiments (Cell Counting Kit-8, flow cytometry and Transwell assays). The targeting relationship between circRNA_0044556 and miR-145 was investigated via bioinformatics analysis, dual-luciferase reporter assay and RNA immunoprecipitation. The effects of the circRNA_0044556/miR-145 axis on the TNBC cells were revealed by rescue experiments. Correlations among circRNA_0044556, miR-145 and NRAS were analyzed by Pearson's correlation test. CircRNA_0044556 was highly expressed in TNBC tissues and cells with or without ADM-resistance. The overexpression of circRNA_0044556 promoted cell viability, ADM-resistance and migration, while inhibiting the apoptosis by sponging miR-145. Upregulation of miR-145 reversed the effects of circRNA_0044556 on the TNBC cells. CircRNA_0044556 was negatively correlated with miR-145 yet positively correlated with NRAS, the target gene of miR-145, in addition to the discovery suggesting the negative regulatory effects of circRNA_0044556 on miR-145. CircRNA_0044556 diminished the sensitivity of TNBC cells to ADM via the miR-145/NRAS axis.

Automated summary

This study reveals that circRNA_0044556 promotes cell viability, ADM resistance, and migration while inhibiting apoptosis in TNBC cells by sponging miR-145. CircRNA_0044556 is negatively correlated with miR-145 and positively correlated with NRAS, indicating its negative regulatory effects on miR-145. Additionally, circRNA_0044556 diminishes the sensitivity of TNBC cells to ADM via the miR-145/NRAS axis.