CT120: A New Potential Target for c-Myc in Head and Neck Cancers

Abstract

Background: CT120 is a universally expressed protein with seven transmembrane domains. It functions in cell proliferation, survival and apoptosis by activating Raf/MEK/ERK and PI3K/Akt signaling pathways. Evidence suggests that CT120 plays important roles in lung carcinogenesis and oncogenic pathway activation. c-Myc is an important transcription factor modulating cell progression, apoptosis and cellular transformation. Previous studies have shown that MYC gene is amplified in many types of cancer including head and neck squamous cell carcinoma (HNSCC). Myc can regulate expression of many genes by binding to E-boxes. The aim of this study was to investigate the relationship between c-Myc protein and CT120 gene.Methods: Tumor and normal tissue samples from 50 patients with HNSCC were investigated with chromatin immunoprecipitation assay (ChIP), Illumina MiSeq, bisulphite sequencing and qRT-PCR.Results: c-Myc binds to all E-boxes except E-box 5 on CT120 promoter. The CpG dinucleotides were found to be partially methylated in all tumor and normal tissue samples. Bisulphite sequencing showed a 10% down-regulation in the methylation levels of the tumor tissues. CT120 gene was hypomethylated and up-regulated in 56% of the tumor tissue samples. Expression of c-Myc was significantly higher in tumor tissues than in non-cancerous tissue samples. MYC was overexpressed in 68% of the tumor tissue samples compared to normal tissues. The mean MYC levels were 2.42-fold higher in the tumor tissue samples. In 48% of the tumor tissues, MYC and CT120A mRNA were up- or down-regulated simultaneously (p<0.001).Conclusion: We show that CT120 gene is a target of c-Myc and it contributes to cancer progression in HNSCC.

FAM57A (Family with Sequence Similarity 57 Member A) Is a Cell-Density-Regulated Protein and Promotes the Proliferation and Migration of Cervical Cancer Cells

“…Thus far, there are scant data available concerning the regulation of FAM57A gene expression. In head and neck cancers, binding of c-Myc to several binding sites (E-boxes) in the FAM57A transcriptional promoter was reported, raising the possibility that the FAM57A gene is a target for activation by the c-Myc oncoprotein [ 38 ]. In addition, silencing expression of the epigenetic regulator EZH2 (enhancer of zeste homolog 2) led to the downregulation of FAM57A transcript levels in colon cancer cells in large scale transcriptome analyses [ 39 ].…”

Integrated Analysis of FAM57A Expression and Its Potential Roles in Hepatocellular Carcinoma

“…As a novel membrane-associated gene, FAM57A has been reported to exert an oncogenic function in lung cancer and head and neck cancers ( 7 – 10 ). However, prior to this study, the expression of FAM57A and its potential roles in HCC were essentially unknown.…”

DataSheet_1.zip

“…These results indicated that FAM57A contributes to lung tumorigenesis. There have also been reports that indicated FAM57A could play an oncogenic role in head and neck squamous cell cancer (9,10). To date, the impact of FAM57A in HCC has rarely been reported.…”