CircEGFR reduces the sensitivity of pirarubicin and regulates the malignant progression of triple-negative breast cancer via the miR-1299/EGFR axis

Abstract

Circular RNAs (circRNAs) have been found to be involved in cancer progression and chemotherapy sensitivity. However, the biological function of circRNAs in triple-negative breast cancer (TNBC) and its effect on the sensitivity to pirarubicin (THP) chemotherapy are still unclear. CircEGFR (hsa_circ_0080220) was screened and verified by bioinformatics analysis, proving it was highly expressed in TNBC cell lines, patient tissues, and plasma exosomes, and was associated with poor prognosis of patients. The expression level of circEGFR in patient tissue has potential diagnostic value to distinguish TNBC tissue from normal breast tissue. In vitro studies confirmed that overexpression of circEGFR promoted the proliferation, migration, invasion, and EMT of TNBC cells and decreased the sensitivity of THP treatment while silencing circEGFR showed the opposite effect. The circEGFR/miR-1299/EGFR pathway was cascaded and verified. CircEGFR regulated malignant progression of TNBC by regulating EGFR via sponging miR-1299. THP can inhibit the malignant phenotype of MDA-MB-231 cells by downregulating the expression of circEGFR. In vivo studies confirmed that overexpression of circEGFR can promote tumor growth and EMT and reduce tumor sensitivity to THP treatment. Silencing circEGFR inhibited the malignant progression of the tumor. These results revealed circEGFR is a promising biomarker for TNBC diagnosis, therapeutic and prognosis.

Keywords: EGFR; Exosome; Pirarubicin; TNBC; circEGFR; miR-1299.