J Cancer 2017; 8(5):880-886. doi:10.7150/jca.18207
CT120: A New Potential Target for c-Myc in Head and Neck Cancers
1. Istanbul University Cerrahpasa Medical Faculty, Department of Medical Biology;
2. Istanbul University Cerrahpasa Medical Faculty, Department of Otorhinolaryngology.
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.
Keywords: CT120, FAM57A, c-Myc, HNSCC, bisulphite, sequencing, methylation.
Baltaci E, Seyhan B, Baykara O, Buyru N. CT120: A New Potential Target for c-Myc in Head and Neck Cancers. J Cancer 2017; 8(5):880-886. doi:10.7150/jca.18207. Available from http://www.jcancer.org/v08p0880.htm