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DNA Methylation and Epigenetics: New Developments in Biology and Treatment
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
Jesus Duque, Michael Lübbert, Mark Kirschbaum
Histone methylation is a marker of both active and inactive genes. Trimethylation of lysine 4 in H3K4 is linked to activated genes (79,80). Methylation at this site is associated with multiple other modifications such as acetylation by acetyltransferases (81) and deacetylation by deacetylases, the latter activity perhaps acting as a brake on genes actively transcribed by H3K4 methylation (82). On the other hand, some H3K4 interactions are specific for unmethylated DNA. The MLL enzymes, which can polymethylate H3K4 (83,84), exist as multicomponent complexes containing differing catalytic SET-related units (85). MLL1 in particular interacts with other modifiers such as the acetylases MOF and CBP (86), and along with other MLL enzymes also recruits the homeobox family genes. The Hox transcription factors play a role in embryonic development, as well as in angiogenesis, in which HoxD3, HoxB3, and HoxA9 are essential regulators. MLL1 is responsible for H3K4 trimethylation at the HoxA9 locus (86). It has recently been shown that suppression of MLL will inhibit Hox-related proangiogenic activity (87). A necessary component of the MLL complex that regulates Hox gene expression is menin, which specifically associates with MLL proteins among SET1 homologs. Menin is the protein encoded by Men1, which when mutated leads to multiple neoplasms, particularly in endocrine tissue (88). Hox gene expression is dependent upon the association of menin with MLL (89).
Overexpression of HOXC10 promotes glioblastoma cell progression to a poor prognosis via the PI3K/AKT signalling pathway
Published in Journal of Drug Targeting, 2019
Yong Guan, Yajie He, Shaoping Lv, Xiaoqun Hou, Luo Li, Jianjun Song
Increasing evidences implicates HOX genes in cancer. Recent studies have demonstrated that HOXD9 contributes to cell proliferation or survival in glioma cells [19]. HOXB3, HOXB4 and HOXC6 are expressed in paediatric medulloblastomas and primitive neuroectodermal tumours [11]. Our finding of HOXC10 regulation in GBM also implies a role for HOXC10 outside the nucleus. Further studies will focus on the mechanism of action of HOXC10 in cancer cells, to understand how HOXC10 mediates its effects on proliferation, apoptosis, and invasive phenotypes. In cervical cancer cells, HOXC10 is associated with increased invasiveness [20]. Thushangi et al. also observed high HOXC10 expression in a subset of primary tumours. In addition, knockdown of HOXC10 reduced growth of T47D cells [21]. Consistent with our research, knockdown of HOXC10 inhibited GBM U87 cell proliferation, migration and invasion. Additionally, such growth-promoting effects of HOXC10 on GBM cells might be involve in the PI3K/Akt pathways.