Epigenetic Silencing of SOX15 Is Controlled by miRNAs rather than Methylation in Papillary Thyroid Cancer.

METHODS: In this study, qRT-PCR was used to investigate the expression levels of the SOX15 gene and of miR-182, miR-183, miR-375, and miR-96 in thyroid tumors and adjacent noncancerous tissues. We also investigated the methylation status of the SOX15 promoter by methylation-specific PCR in tumors and adjacent noncancerous tissues. RESULTS: We observed a statistically significant downregulation of SOX15 expression in tumors compared to noncancerous tissue samples. The methylation levels of tumors and matched noncancerous tissues were similar, but miR-182, miR-183, and miR-375 expression levels were elevated in tumor tissues compared to noncancerous tissue samples. CONCLUSIONS: Our results indicate that SOX15 gene expression is associated with the pathogenesis of papillary thyroid carcinoma (PTC), and the epigenetic control of the SOX15 gene is regulated by miRNAs rather than by promoter methylation.

Silencing of Wwox Increases Nuclear Import of Dvl proteins in Head and Neck Cancer.

Background: Wnt signaling pathway is associated with a variety of human cancers, including HNSCC. Wnt proteins control cellular events such as proliferation, fate specification, polarity, and migration by transducing signals to the nucleus through several cytoplasmic relay proteins. Although activation of the Wnt/ß-catenin pathway is a frequent event in various cancers, there is limited knowledge on the contribution of this signaling mechanism in HNSCC. The Wwox tumor suppressor protein participates in the regulation of Wnt signaling by interacting with Dvl proteins. Methods: In this study, we used qRT-PCR and western blotting to examine the mRNA and protein levels of the Dvls in association with WWOX in HNSCC cell lines and tumor tissues. Results: We found that silencing of WWOX leads to increased nuclear localization of the Dvl proteins in cell lines. However, we detected an increase only in the nuclear localization of Dvl-1 in tumor tissues. Conclusions: Our results suggest that aberrant WWOX expression contributes to HNSCC through the Wnt signaling pathway. Decreased expression of WWOX may function in HNSCC progression by allowing the nuclear localization of Dvl proteins.

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

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.