CircATXN7 contributes to the progression and doxorubicin resistance of breast cancer via modulating miR-149-5p/HOXA11 pathway.

ABSTRACT

Breast cancer is a frequent tumor threatening the health of women. Circular RNAs (circRNAs) play vital roles in cancer progression and chemoresistance. Herein, we mainly investigate the role and potential mechanism of circRNA ataxin 7 (circATXN7; circ_0066436) in breast cancer. RNA expression levels were detected via quantitative real-time PCR (qPCR), western blot and immunohistochemistry. Cell viability and half inhibitory concentration (IC50) of doxorubicin were assessed by cell counting kit-8 (CCK-8) method. Cell proliferation, migration and invasion were determined by CCK-8, 5-ethynyl-2'-deoxyuridine, colony formation and transwell assays. The binding relationship between microRNA-149-5p (miR-149-5p) and circATXN7 or homeobox A11 (HOXA11) was validated via dual-luciferase reporter assay and RNA immunoprecipitation assay. Xenograft assay was conducted to analyze the effect of circATXN7 on doxorubicin resistance of breast cancer. CircATXN7 and HOXA11 levels were enhanced, whereas miR-149-5p level was declined in breast cancer tissues and cells. CircATXN7 silencing suppressed breast cancer development and doxorubicin resistance. Additionally, circATXN7 upregulated HOXA11 via absorbing miR-149-5p, thereby inducing breast cancer cell progression and reducing doxorubicin sensitivity. Besides, depletion of circATXN7 enhanced doxorubicin sensitivity in vivo. Interference of circATXN7 inhibited breast cancer progression and doxorubicin resistance via mediating miR-149-5p/HOXA11 axis, which might provide a possible biomarker for breast cancer therapy.