Inhibition of XIST restrains paclitaxel resistance in breast cancer cells by targeting hsa-let-7d-5p/ATG16L1 through regulation of autophagy

Abstract

Breast cancer is a fatal malignant tumor in women worldwide. The development of paclitaxel resistance remains a challenge. Autophagy is considered to have a significant part in the chemotherapeutic stress mechanism. This study aimed to investigate the function of long non-coding RNA (lncRNA) in breast cancer cell chemoresistance and autophagy. The paclitaxel (PTX)-resistant breast cancer cells were established. The function of X-inactive specific transcript (XIST) was demonstrated using in vitro and in vivo experiments. Transmission electron microscope (TEM) was used to observe autophagy vesicles. Protein and mRNA levels were determined using western blotting and quantitative real time polymerase chain reaction (qRT-PCR). We discovered that autophagic activity was correlated with chemoresistance in PTX-resistant breast cancer cells. In vitro and in vivo studies showed that XIST inhibition reduced cell resistance to paclitaxel, caused autophagy to be suppressed by regulating hsa-let-7d-5p and ATG16L1 expression. Mechanically, threonine protein kinase B (PKB; also known as AKT) - mammalian target of rapamycin (mTOR) pathway was activated when knockdown of XIST, while was reversed by inhibition of hsa-let-7d-5p. Our results verified that XIST played a significant role in developing chemoresistance via mediating autophagy in PTX-resistant breast cancer cells. It may be a potential target for breast cancer treatment strategies.