Abstract
The homeobox (HOX) genes encoding an evolutionarily highly conserved family of homeodomain-containing transcriptional factors are essential for embryogenesis and tumorigenesis. HOX genes are involved in cell identity determination during early embryonic development and postnatal processes. The deregulation of HOX genes is closely associated with numerous human malignancies, highlighting the indispensable involvement in mortal cancer development. Since most HOX genes behave as oncogenes or tumor suppressors in human cancer, a better comprehension of their upstream regulators and downstream targets contributes to elucidating the function of HOX genes in cancer development. In addition, targeting HOX genes may imply therapeutic potential. Recently, novel therapies such as monoclonal antibodies targeting tyrosine receptor kinases, small molecular chemical inhibitors, and small interfering RNA strategies, are difficult to implement for targeting transcriptional factors on account of the dual function and pleiotropic nature of HOX genes-related molecular networks. This paper summarizes the current state of knowledge on the roles of HOX genes in human cancer and emphasizes the emerging importance of HOX genes as potential therapeutic targets to overcome the limitations of present cancer therapy.
Highlights
1.1 General OverviewThe homeobox (HOX) genes were initially discovered in 1992 with the roles in embryogenesis in Drosophila melanogaster, where mutations in antennapedia and bithorax clusters were observed to lead to abnormal body development [1]
It indicates the prospective potency of HOXA transcript at the distal tip (HOTTIP) and HOXA13 to be the predictive biomarker in hepatocellular carcinoma (HCC) [163]
It is difficult to intercept various transcription factors, alternative strategies based on the exploitation of the associated molecular networks are emerging
Summary
The homeobox (HOX) genes were initially discovered in 1992 with the roles in embryogenesis in Drosophila melanogaster, where mutations in antennapedia and bithorax clusters were observed to lead to abnormal body development [1]. These mutations lead one body segment to emerge similar to another segment and is originally called the term “homeotic” mutations since the 1990s [2]. The HOX genes encode a family of transcription factors that regulate embryogenesis and morphogenesis during the embryonic period and adulthood These genes are highly conserved and contain homologous domains in almost all eukaryotic cells [3]. Each cluster has between 9 and 11 genes in a row on a homologous strand of DNA, which contains duplication and divergence of ancestral HOX genes
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