HOX genes act as transcription factors which regulate embryonic development. They are a subgroup of the homeobox. In the human genome there are 39 HOX genes in four chromosomal clusters. Spatial collinearity, posterior prevalence, and temporal collinearity are the three principals that HOX genes express and control the development process. In cells, HOX proteins play a major role in apoptosis, cell proliferation, and receptor signaling. In cancers, HOX genes act as transcriptional repressors and also transcriptional activators. Three principals of HOX genes deregulation in cancers are classified as temporospatial deregulation, epigenetic deregulation, and gene dominance. HOX genes are altered by overexpression, methylation of the promoter and downregulation and change their expression patterns in cancers. Altered expression of HOX genes are a cause for lung carcinoma, ovarian carcinoma, prostate carcinoma, and breast carcinoma etc. miRNAs and ncRNAs are also important in the regulation of the gene expression of the HOX genes and altered amounts of miRNAs and ncRNAs can lead to cancers. Some HOX genes have been investigated as biomarkers in cancer conditions.

1. HOX GENES
AND THEIR
ROLE IN
CANCERS.
By Pasan Wijesinghe.
154397

2. JensMartensson
2
Contents
1. What is cancer
2. What are HOX genes
3. General overview of the HOX gene
structure
4. HOX gene expression and regulations
5. HOX genes deregulation in cancers
6. Expressions of HOX genes in cancers
7. HOX genes and therapies
8. Conclusion
9. References

3. JensMartensson
Cancers are set of diseases characterized by unregulated cell
growth leading to invasion of surrounding tissues and spread
to other parts of the body.
• Cancer cells are able to ignore signals like apoptosis.
• Cancer cells may influence the normal cells, blood
vessels, molecules which are known as micro-
environment.
What is a cancer
3
Cancer cell division.

4. JensMartensson
• Cancer cells are also often able to evade the
immune system and it can change the normal
function of the cell.
• Cancers are genetically instable.
What is a cancer
4

5. JensMartensson
5
What are HOX
genes.
HOX genes act as transcription
factors to regulate the embryonic
development.
• Transcription factor (TF) is a protein that
controls the rate of transcription
of genetic information from DNA
to mRNA by binding to a specific DNA
sequence.
• HOX genes first identified by homeotic
mutations in the fruit fly Drosophila
melanogaster.
HOX genes

6. JensMartensson
6
What are HOX genes.
• HOX genes are important in regulating apoptosis,
receptor signaling and metabolic pathways.
• In human genome there are 39 total HOX genes
in four chromosomal clusters.
• Those four clusters are named as HOXA, HOXB,
HOXC and HOXD.
• HOX gens consists of 200 bases to several
kilobases.
• Two exons and a single intron can be found in
HOX gene.

7. JensMartensson
• Purple color region indicate the promotor
region of the HOX gene.
• 5’ and 3’ UTR region is indicated in grey color
region
• Exon1 and exon 2 in the gene indicated in the
green color region.
• Intron in the gene indicate in the red color
region.
• Homeodomain indicate in the blue color region
General overview of the HOX gene
structure
7

8. JensMartensson
There are three principles that HOX genes express and control the
development process.
• Spatial collinearity
HOX genes which are situated in chromosomal clusters, 3’ genes expressed in anteriorly and
5’genes expressed in posteriorly in embryonic development.
• Posterior prevalence
Genes which are located at 5' in clusters dominant to gens which located in 3’.
HOX gene expression and regulation
8

9. JensMartensson
• Temporal collinearity.
In each cluster, HOX genes are express temporally in 3' to 5' direction.
HOX gene expression and regulation
9
HOX gene expression pattern in human

10. JensMartensson
In cancers deregulation of HOX genes can mainly classified into three
mechanisms.
• Temporospatial deregulation
Expression of 5' HOX genes is much higher than the expression of 3' HOX genes in those
types of cancerous tissues.
• Gene dominance
The expression of specific HOX genes in cancerous tissue is much higher in comparison
with the normal tissues. There is a relationship between the XOH gene dose and its effect.
Within some doses, HOX genes help for the oncogenesis in that same tissue.
HOX gene deregulation in cancers
10

11. JensMartensson
• Epigenetic deregulation
Histone modification and methylation change the expression pattern of HOX genes. It will
activate Anti-apoptosis pathways and finally leads to cancers
HOX gene deregulation in cancers
11

12. JensMartensson
• Specific pattern of change in HOX gene
expression is dependent on cancer type,
tumor stage and anatomic location.
• Aberrant HOX genes expression could
contribute to oncogenesis by allowing
activation of anti-apoptosis pathways.
• Many HOX genes were to be aberrantly
expressed in multiple different cancer
types.
Expression of HOX genes in cancers
12

13. JensMartensson
• There are HOX gene regulatory networks
which are functionally associated in
metabolic pathways, signaling pathways
through protein-protein interactions and
through physical interactions.
• In cancer conditions those regulatory
networks associate with HOX genes
which are express aberrantly with other
genes.
Expression of HOX genes in cancers
13
Eg:-HOXD8, HOXD4, HOXB7, HOXB6,
HOXB9,HOXD12 and HOXB13 genes
expressed aberrantly in colon cancers

14. JensMartensson
• HOX genes can use as biomarkers to identify the cancers.
• Study about the non coding RNA, micro RNA in HOX gene regulation , their role and
expression in cancer can be important for the drug discovery.
Eg- A549 lung cancer cells can undergo apoptosis by blocking the activity of HOX
genes.
HOX genes and therapies.
14

15. JensMartensson
• Differential expression of the HOX genes in various tumors provides an opportunity to
advance our understanding of cancer development.
• Studying the regulatory mechanisms in solid tumors can provide the new targets for
effective cancer therapeutics.
• Future studies need to address whether changes in HOX genes expressions are a cause or
contributor to carcinogenesis or an effect of carcinogenesis.
Conclusion
15

16. JensMartensson
• Shah, N.; Sukumar, S. The Hox Genes and Their Roles in Oncogenesis. Nat. Rev. Cancer 2010
• Grier, D. G.; Thompson, A.; Kwasniewska, A.; McGonigle, G. J.; Halliday, H. L.; Lappin, T. R. The
Pathophysiology of HOX Genes and Their Role in Cancer. J. Pathol. 2005
• Montavon, T.; Soshnikova, N. Hox Gene Regulation and Timing in Embryogenesis. Semin. Cell Dev. Biol.
2014.
• Seifert, A. Role of Hox Genes in Stem Cell Differentiation. World J. Stem Cells 2015
• Lappin, T. R. J.; Grier, D. G.; Thompson, A.; Halliday, H. L. HOX Genes: Seductive Science, Mysterious
Mechanisms. Ulster Med. J. 2006
Reference
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17. Thank You
Pasan Wijesinghe.