PDK1-stabilized LncRNA SPRY4-IT1 promotes breast cancer progression via activating NF-κB signaling pathway.

Abstract

Pyruvate dehydrogenase kinase 1 (PDK1)is a widely known glycolytic enzyme, and some evidence showed that PDK1 promoted breast cancer by multiple approaches. However, very few lncRNAs have been identified to be associated with PDK1 in breast cancer in previous research. In this study, we found that lncRNA sprouty4-intron transcript 1 (SPRY4-IT1)was regulated by PDK1 with correlation analysis, and PDK1 upregulated SPRY4-IT1remarkably in breast cancer cells, as PDK1 interacted with SPRY4-IT1in the nucleus and significantly enhanced the stability of SRPY4-IT1.Furthermore, SPRY4-IT1was highly expressed in breast cancer, significantly promoted the proliferation and inhibited apoptosis of breast cancer cells. In terms of mechanism, SPRY4-IT1inhibited the transcription of NFKBIA and the expression of IκBα, thus promoting the formation of p50/p65 complex and activating NF-κBsignaling pathway, which facilitated survival of breast cancer cells. Therefore, our finding reveals that PDK1/SPRY4-IT1/NFKBIA axis plays a crucial role that promoting tumor progression, and SPRY4-IT1knockdown incombined with PDK1 inhibitor is promising to be a new therapeutic strategy in breast cancer.