Knockdown of ectodysplasin‑A receptor‑associated adaptor protein exerts a tumor‑suppressive effect in tongue squamous cell carcinoma cells

Abstract

Tongue squamous cell carcinoma (TSCC) is a common malignancy in oral cancer with a high mortality and morbidity. The ectodysplasin-A receptor-associated adaptor protein (EDARADD) is a death domain-containing adaptor protein that interacts with the TNF family ligand ectodysplasin A receptor. It is known that EDARADD has an effect on the development of ectodermal derivative tissues, such as hair and teeth. EDARADD expression is also associated with the development of melanoma. However, the role of EDARADD in TSCC remains unknown. The aim of the present investigation was to explore whether EDARADD plays a role in the biological function of TSCC. Immunohistochemistry was used to measure the expression of EDARADD in TSCC tissues and adjacent normal tissue. EDARADD was knocked down in a TSCC cell line in vitro using a specific lentivirus. The expression level of the EDARADD gene and the efficacy of gene knockdown were evaluated by reverse transcription-quantitative PCR, while EDARADD protein expression and the expression levels of Bcl-2, MYC and NF-κBp65 were determined by western blotting. Additionally, MTT assays, colony formation assays and apoptosis assays were carried out to examine the effect of EDARADD knockdown on the TSCC cells. A previous study showed that the majority of the TSCC tissues that were tested had high EDARADD expression. The expression of EDARADD both at mRNA and protein levels was significantly lower (P<0.01) after the gene was knocked down in the CAL27 cells compared with the level in control cells. Downregulation of EDARADD expression inhibited colony formation and proliferation and induced apoptosis of CAL27 cells when compared to control cells (P<0.01). Taken together, these results suggested that EDARADD may be actively involved in the progression of TSCC and that EDARADD may be a novel therapeutic target for the treatment of TSCC.

RNA Sequencing Analysis Reveals Divergent Adaptive Response to Hypo- and Hyper-Salinity in Greater Amberjack (Seriola dumerili) Juveniles

“…Moreover, hypo-salinity down-regulated edar and tnfsf12 mRNA in greater amberjack. Studies have shown that EDAr (ectodysplasin A receptor), belonging to the tumor necrosis factor receptor (TNFr) superfamily, can regulate cell activities, such as differentiation, proliferation, maturation, and lipid metabolism, by binding to the ectodysplasin A1 (EDA1) [68][69][70][71]. A previous study showed that tnfsf12 (TNF superfamily member 12) can inhibit lipid deposition in a dose-dependent manner without any cytotoxic effects.…”

Ectodysplasin A/Ectodysplasin A Receptor System and Their Roles in Multiple Diseases

“…In vivo , the tumor burden of mice transplanted with shEDAR-transduced tumor cells was significantly alleviated, and the tumor volume of EDAR-deficient mice was less than 1,000 mm 3 . In addition, Li et al (2020) showed that EDARADD was highly expressed in head and neck squamous cell carcinoma (HNSCC) tissues while EDARADD expression was associated with the degree of tumor differentiation and local recurrence in tongue squamous cell carcinoma (TSCC). Furthermore, EDARADD knockdown in TSCC cells affected clonogenicity, induced apoptosis, suppressed proliferation, and reduced the expression of NF-κBp65, MYC, and Bcl-2.…”

“…In patients with non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), the plasma EDA content is high and is associated with deteriorating steatosis and fibrosis ( Bayliss et al, 2021 ). In addition to the effects on HED and metabolic disorders, several studies have reported that EDA and its receptors are involved in cancer pathogenesis by regulating the apoptosis, proliferation, differentiation, and migration of cancer cells ( Soraas and Stebbing, 2018 ; Vial et al, 2019 ; Li et al, 2020 ; Wang et al, 2020 ); however, this possibility remains controversial. Here, we review the role of EDA and its two-receptor system in various signaling pathways and then discuss the physiological and pathological roles associated with EDA and its receptors.…”

Ectodysplasin A Is Increased in Non-Alcoholic Fatty Liver Disease, But Is Not Associated With Type 2 Diabetes

“…The EDA transcript is alternatively spliced producing different isoforms, with EDA-A1 and EDA-A2 being dominant and differing by only two amino acids. EDA is a type II membrane protein that can be cleaved by furin to produce a secreted form (10)(11)(12), which is subsequently recognized by the ectodysplasin A receptor (10,(13)(14)(15). EDA acts as a homotrimer and plays an important role in the development of ectodermal tissues such as skin (16,17).…”