Expression Analysis of BIRC3 as One Target Gene of Transcription Factor NF-κB for Esophageal Cancer

Abstract

Esophageal cancer (ESCA) is one of the highest lethal malignancy tumors worldwide. Baculoviral IAP repeat-containing protein 3 (BIRC3) is the main inhibitor of apoptosis in many malignancies. The aim of this study was to clarify how BIRC3 acts in ESCA cells. Through TNMplot and GEPIA2 analysis, BIRC3 was found abundantly expressed in ESCA cells. The quantitative RT-PCR assay confirmed BIRC3 was pronouncedly induced in all used ESCA cell lines. In addition, proinflammatory cytokines TNFα and IL-1β were shown to have promotion effects on BIRC3 expression in ESCA cells. These promotive effects were blocked when the function of NF-κB was inhibited by bay 11-7082, which indicates the expression of the BIRC3 gene was regulated via the NF-κB transcription pathway in ESCA. Moreover, bioinformatics analysis showed that the BIRC3 gene had many NF-κB binding cis-elements. Chromatin immunoprecipitation was then performed and it was found that NF-κB directly interacts with cis-elements of the BIRC3 gene. In conclusion, our data proved that the high expression level of BIRC3 maintained the survival of ESCA cells. BIRC3 was up-regulated by proinflammatory cytokine TNFα and IL-1β through the NF-κB signaling pathway, and this may be helpful for esophageal cancer prevention and therapy.