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Epigenetic regulation of homeobox genes in liver cancer
Author(s) -
Liu Hongyan,
Robertson Keith,
Liu Chen
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.794.12
Homeobox genes belong to a family of transcription factors that determine the identity of cells and tissues during normal development. They contain the homeobox, a 183 bp DNA sequence coding for a 61 amino acid DNA‐binding domain. Differential expression of HOX genes has been noticed in normal and cancer cells, which suggests their role in carcinogenesis. Epigenetic regulation has been implicated in the control of the HOX gene regulation. The objective of our study is to investigate epigenetic regulation of HOX genes in hepatocellular carcinoma (HCC). We have examined the expression profile of all the known members of HOX gene family in both HCC cell lines and HCC cancer tissues. In the cell line experiment, we found that many HOX genes are regulated by epigenetic modification, as determined by treatment with 5‐aza‐2′‐deoxycytidine and Trichostatin A. Moreover, alcoholic treatment and hepatitis C infection also affected the expression of several HOX genes in primary hepatocytes. In HCC tissue analysis, we found that that HOX B4 was down‐regulated in 7 out of 18 of cancerous tissues compared with non‐cancerous tissues in patients with HCC and HOX C13 was reduced in 10 out of 18 of tumor tissues, while HOX A13 was up‐regulated in the majority of HCC cancer tissues. We further examined the function of HOX A13 in HCC cell lines and found that HOX A13 promoted cell proliferation. Our results suggest that HOX gene is controlled by epigenetic mechanism, which may be directly involved in the pathogenesis of HCC. Research support: this work is partially supported by NIH grants R01CA133086 and K26RR023976 to CL.