NLRP3 inflammasome inactivation driven by miR‑223‑3p reduces tumor growth and increases anticancer immunity in breast cancer.

Abstract

MicroRNA-233-3p (miR-223-3p) is considered an important cancer-associated marker. The NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome represents a novel potential target for the treatment of breast cancer. Therefore, it was hypothesized that miR-223-3p may affect tumor growth and immunosuppression in breast cancer by inhibiting the NLRP3 inflammasome. In the present study, an increased expression level of NLRP3 was detected in three breast cancer cell lines compared with normal mammary epithelial cells (HMEC). Suppressing the expression of NLRP3 in MCF-7 cell lines increased the apoptotic rate of breast cancer cells and reduced the proliferative capacity. NLRP3 was identified to be a direct target of miR-233-3p using a luciferase assay. In addition, miR-233-3p mimics inhibited the NLRP3-dependent processes in cancer cells by suppressing the NLRP3 expression level and the protein expression levels of its downstream factors, including PYD and CARD domain containing protein, interleukin-1β and interleukin-18. In vivo experiments demonstrated the suppressive effect of miR-233-3p in tumor growth and immunosuppression. Collectively these findings suggested that the inactivation of the NLRP3 inflammasome driven by miR-223-3p reduced the growth and immunosuppression of breast cancer in vitro and in vivo, and may represent a novel therapeutic strategy in treating breast cancer.