RELA is required for CD271 expression and stem-like characteristics in hypopharyngeal cancer

Abstract

CD271 (also referred to as nerve growth factor receptor or p75NTR) is expressed on cancer stem cells in hypopharyngeal cancer (HPC) and regulates cell proliferation. Because elevated expression of CD271 increases cancer malignancy and correlates with poor prognosis, CD271 could be a promising therapeutic target; however, little is known about the induction of CD271 expression and especially its promoter activity. In this study, we screened transcription factors and found that RELA (p65), a subunit of nuclear factor kappaB (NF-κB), is critical for CD271 transcription in cancer cells. Specifically, we found that RELA promoted CD271 transcription in squamous cell carcinoma cell lines but not in normal epithelium and neuroblastoma cell lines. Within the CD271 promoter sequence, region + 957 to + 1138 was important for RELA binding, and cells harboring deletions in proximity to the + 1045 region decreased CD271 expression and sphere-formation activity. Additionally, we found that clinical tissue samples showing elevated CD271 expression were enriched in RELA-binding sites and that HPC tissues showed elevated levels of both CD271 and phosphorylated RELA. These data suggested that RELA increases CD271 expression and that inhibition of RELA binding to the CD271 promoter could be an effective therapeutic target.

Has-miR-199a-3p/RELA/SCD inhibits immune checkpoints in AMD and promotes macrophage-mediated inflammation and pathological angiogenesis through lipid metabolism pathway: A computational analysis

“…The research results show that RELA can regulate the expression of CD47 and promote the production of microenvironment for immune escape [ 44 ]. It has been reported that RELA-controlled genes can regulate many biological processes, such as innate and acquired immunity, inflammation, stress response, B-cell formation, and lymphogenesis [ 45 ]. A previous study showed that SCD was involved in endoplasmic reticulum stress, autophagy, ferroptosis, apoptosis and inflammation [ 37 ].…”

LncBIRC3-OT promotes the malignant progression of glioma by interacting with RELA to upregulate stanniocalcin-1 expression

“…RELA acts as a transcription factor that enhances the expression of multiple proliferation- or migration-related gene in tumors [ 37 , 38 ]. For example, RELA activates lncRNA NEAT1, which promotes the malignant behavior of pancreatic ductal adenocarcinoma cells [ 39 ].…”

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“…Among its related pathways are MyD88 dependent cascade initiated on endosome and bacterial infections in cystic fibrosis (CF) airways. 30 Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and identical Diseases associated with EP300 include Rubinstein-Taybi syndrome 2 and Menke-Hennekam syndrome 2 (MKHK2). Among its related pathways are RNA polymerase I promoter opening and regulation of activated PAK-2p34 by proteasome mediated degradation.…”