HOPX functions as a tumour suppressor in head and neck cancer

Abstract

Head and neck squamous cell carcinoma (HNSCC) is generalized term that encompasses a diverse group of cancers that includes tumours of the oral cavity (OSCC), oropharynx (OPSCC) and nasopharynx (NPC). Genetic alterations that are common to all HNSCC types are likely to be important for squamous carcinogenesis. In this study, we have investigated the role of the homeodomain-only homeobox gene, HOPX, in the pathogenesis of HNSCC. We show that HOPX mRNA levels are reduced in OSCC and NPC cell lines and tissues and there is a general reduction of HOPX protein expression in these tumours and OPSCCs. HOPX promoter methylation was observed in a subset of HNSCCs and was associated with a worse overall survival in HPV negative tumours. RNAseq analysis of OSCC cells transfected with HOPX revealed a widespread deregulation of the transcription of genes related to epithelial homeostasis and ectopic over-expression of HOPX in OSCC and NPC cells inhibited cell proliferation, plating efficiency and migration, and enhanced sensitivity to UVA-induced apoptosis. Our results demonstrate that HOPX functions as a tumour suppressor in HNSCC and suggest a central role for HOPX in suppressing epithelial carcinogenesis.

HOPX homeobox methylation in differentiated thyroid cancer and its clinical relevance

“…Approximately half of the patient samples studied did find a similar pattern to that reported for other cancers ( 8 , 10 , 11 , 12 , 13 ). The fact that in this study and others ( 10 , 19 , 25 ) several samples did not show a clear correlation between methylation values and expression suggests that reduction of HOPX-β mRNA could be partially explained by epigenetic alterations, though HOPX-β promoter methylation is one of mechanism for inactivation. In evaluating HOPX-β mRNA expression in benign tumors and their adjacent non-tumor samples, four of six paired samples showed reduced tumor expression, an extended study using a larger sample is necessary to confirm HOPX-β mRNA expression levels in benign tumors.…”

“…The HOPX methylation beta values from TCGA data (level 2) ( 24 ) were collected from Xena Public Data Hubs ( https://xena.ucsc.edu/ ). From the 25 HOPX CpG sites with methylation data, six CpG sites within the CpG island of the HOPX-β promoter were considered relevant and the methylation value of the island was calculated as the sum of their beta values ( 25 ). To categorize T samples as hyper-methylated threshold methylation value of 1.89 was determined considering the distribution of the beta value for normal and T samples as previously described ( 25 ).…”

Knockdown of LINC01116 inhibits cell migration and invasion in head and neck squamous cell carcinoma through epithelial‐mesenchymal transition pathway

“…Numerous studies in recent years have shown a significant correlation between lncRNAs and tumor development and progression, 17,18 and identification of novel lncRNA-based prognostic and therapeutic targets is currently a fervent topic in cancer research. 21 OSCC and NPC are the two main types of HNSCC, 22 and LINC01116 was dramatically upregulated in both types compared with the adjacent normal tissues. The microarray results were successfully F I G U R E 2 The expression level and prognostic significance of the identified lncRNAs in HNSCC.…”

Effect of radiotherapy on the chemical composition of root dentin

“…Each year, there is an estimated 416.05 new cases of cancer per 100 000 inhabitants, wherein the head and neck cancer represents approximately 13.6%, ranking seventh in the world, with an estimated annual incidence of 640 000 cases . Head and neck cancer comprises a heterogeneous group of tumors affecting the oral cavity, larynx, pharynx, thyroid, lips, mouth, nasal cavity, paranasal sinuses, and salivary glands …”