Stat5 inhibits NLRP3-mediated pyroptosis to enhance chemoresistance of breast cancer cells via promoting miR-182 transcription.

The treatment of breast cancer (BC) calls for targeted methods to overcome chemoresistance (CR). This study is expected to figure out the mechanism of signal transducer and activator of transcription 5 (STAT5) in NOD-like receptor family pyrin domain containing 3 (NLRP3)-mediated pyroptosis and CR in BC cells. BC cell lines resistant to paclitaxel (PTX) and cis-diamminedichloro-platinum (DDP) were prepared. Expressions of Stat5, miR-182, and NLRP3 were detected. The 50% inhibition concentration (IC ), proliferation, colony formation, apoptosis rate, and levels of pyroptosis-related factors were appraised and determined. The binding relationships of Stat5 and miR-182, and miR-182 and NLRP3 were testified. Stat5 and miR-182 were highly expressed in drug-resistant BC cells. Silencing Stat5 reduced proliferation and colony formation of drug-resistant BC cells, coincided with elevated levels of pyroptosis-related factors. Stat5 bound to the promoter region of miR-182 to promote miR-182 expression. miR-182 inhibition reversed the role of silencing Stat5 in BC cells. miR-182 inhibited NLRP3. Overall, Stat5 bound to the promoter region of miR-182 to promote miR-182 expression and inhibit NLRP3 transcription, thereby suppressing pyroptosis and enhancing CR of BC cells.