Supplementary Table from LncRNA Uc003xsl.1-Mediated Activation of the NFκB/IL8 Axis Promotes Progression of Triple-Negative Breast Cancer
Funding
National Science and Technology Major Project
National Natural Science Foundation of China
Guangdong Basic and Applied Basic Research Foundation
Guangdong province Science and Technology Plan Foundation
Guangzhou Science and Technology Major Program
Guangdong Science and Technology Department
Sun Yat-sen University
Sun Yat-sen Clinical Research Cultivating Program
Sun Yat-sen Memorial Hospital
China Postdoctoral Science Foundation
ARTICLE ABSTRACT
Aberrant activation of NFκB orchestrates a critical role in tumor carcinogenesis; however, the regulatory mechanisms underlying this activation are not fully understood. Here we report that a novel long noncoding RNA (lncRNA) Uc003xsl.1 is highly expressed in triple-negative breast cancer (TNBC) and correlates with poor outcomes in patients with TNBC. Uc003xsl.1 directly bound nuclear transcriptional factor NFκB-repressing factor (NKRF), subsequently preventing NKRF from binding to a specific negative regulatory element in the promoter of the NFκB-responsive gene IL8 and abolishing the negative regulation of NKRF on NFκB-mediated transcription of IL8. Activation of the NFκB/IL8 axis promoted the progression of TNBC. Trop2-based antibody–drug conjugates have been applied in clinical trials in TNBC. In this study, a Trop2-targeting, redox-responsive nanoparticle was developed to systematically deliver Uc003xsl.1 siRNA to TNBC cells in vivo, which reduced Uc003xsl.1 expression and suppressed TNBC tumor growth and metastasis. Therefore, targeting Uc003xsl.1 to suppress the NFκB/IL8 axis represents a promising therapeutic strategy for TNBC treatment.
These findings identify an epigenetic-driven NFκB/IL8 cascade initiated by a lncRNA, whose aberrant activation contributes to tumor metastasis and poor survival in patients with triple-negative breast cancer.
