Silencing KPNA2 inhibits IL-6-induced breast cancer exacerbation by blocking NF-κB signaling and c-Myc nuclear translocation in vitro

Abstract

Aims: Recently, studies indicated that inflammation could exacerbate the development of BC. Karyopherin α-2 (KPNA2) is a molecule which modulates nucleocytoplasmic transport and is involved in malignant cellular behavior and carcinogenesis. Our study aims to elucidate the role of KPNA2 in BC pathogenesis and explore the mechanism of KPNA2 in regulating inflammation-induced BC exacerbations.

Main methods: We measured the expression of KPNA2 in BC cells. Through loss-of-function experiments, the functional role of KPNA2 in MCF-7 and MDA-MB-468 cells was evaluated. SK-BR-3 cells were treated with IL-6 as an inflammatory in vitro model of BC. ELISA determination exhibited the contents of cytokines. RANKL and leptomycin B treatments activated NF-κB signaling and inhibited the nuclear translocation of c-Myc, respectively.

Key findings: The results showed that KPNA2 was significantly up-regulated in BC and silencing KPNA2 inhibited the proliferation, migration and invasion of BC cells, while the cycle arrest was induced, via blocking NF-κB signaling and c-Myc nuclear translocation. IL-6 stimulated the secretions of IL-8 and IL-17 in BC cells, and elevated KPNA2 expression. However, KPNA2 knockdown suppressed the inflammatory responses and malignant progression of BC induced by IL-6.

Significance: In conclusion, our study illustrated that KPNA2 regulated BC development, as well as IL-6-induced inflammation and exacerbation, via NF-κB signaling and c-Myc nuclear translocation. This may provide a novel target for BC therapy.

Keywords: Breast cancer; Inflammation; KPNA2; NF-κB signaling; c-Myc translocation.