Abstract
Recent decades have witnessed the publication of numerous studies reporting alterations in the genome and transcriptome of head and neck squamous cell carcinoma (HNSCC). Currently, the utilisation of these alterations as biomarkers and targets for therapy is limited and new, useful molecular characteristics are being sought. Many of the published HNSCC gene expression profiles demonstrate alterations in the expression of HOX genes. These are a family of Homeobox-containing genes which are involved in developmental patterning and morphogenesis in the embryo, and which are often aberrantly expressed in cancer. The 39 HOX genes found in the human genome are arranged in four paralogous groups at different chromosomal loci. These control a wide range of cellular processes, including proliferation and migration, which are relevant in the context of cancer development. In this review article, we will outline the biology of HOX genes in relation to cancer and summarise the accumulating evidence for their role in the development of HNSCC and the possibility that they could be a therapeutic target in this malignancy. We will also identify areas where our current understanding is weak to focus future work and appraise the ongoing strategies for pharmacological intervention.
Highlights
In 1894, William Bateson described structural variations and body part replacement/transformations in insects, and named this phenomenon "homeosis" [1]
The regulatory mechanisms of the HOX loci miRNAs generally remain unclear, we have shown that miR196a can be expressed in a polycistronic transcript that includes HOXB9 and possibly other B cluster genes [32], which may indicate a direct link between the altered expression of HOX genes and their corresponding microRNAs in cancer
HOXA10 expression has been studied In head and neck squamous cell carcinoma (HNSCC) by Yamatoji and co-workers [94]. Their findings suggest that HOXA10 is overexpressed in HNSCC and associated with cancer stage, implying that its up-regulation may result in a disease progression
Summary
The expression of HOX genes is highly organized along the antero-posterior axis in patterns termed spatial and temporal collinearity. An overall screen of DNA methylation in oral cancer cells showed increased methylation at sites within the HOX clusters [28], and this was further explored in the HOXB cluster, with re-expression of HOXB4 after treatment with DNA-methyl-transferase inhibitors [29] These changes have been linked to alterations in the activity of polycomb repressive complexes (PRCs) that can control HOX gene expression [30]. There is accumulating evidence that a number of long non-coding RNAs, such as HOTAIR, have pro-tumourigenic effects in many cancers including HNSCC [37], some of which may be mediated by alterations in HOX gene expression and activity. The regulatory mechanisms of the HOX loci miRNAs generally remain unclear, we have shown that miR196a can be expressed in a polycistronic transcript that includes HOXB9 and possibly other B cluster genes [32], which may indicate a direct link between the altered expression of HOX genes and their corresponding microRNAs in cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
