Polycomb group proteins and their role in glioblastoma malignancy

Glioblastoma multiforme (GBM) is one of the most common and aggressive malignant brain tumors in adults. GBMs have proven to be difficult to treat, as they extensively infiltrate to healthy tissue and have insufficient response to treatments. This is caused by GBM tumors being able to resist chemo- and radiation therapy, as well as their intratumoral heterogeneity. Current treatment methods have proven only modestly effective, with median survival of patients diagnosed with GBM being a little over a year. Therefore novel treatments for GBMs must be researched. Epigenetic alterations have been reported to play an important role in GBM development and maintenance. The precise control of gene expression is vital for normal cell function and development. Modifications in chromatin structure and histones are essential in controlling gene expression. Polycomb repressive complexes (PRC) are chromatin modifiers comprised of a conserved family of epigenetic regulators called polycomb group (PcG) proteins. PRCs effect the chromatin structure through post-translational histone modification. They usually function as gene repressors with complexes having their own roles. PRCs are categorized depending on their core and accessory subunits. PcG proteins can also function independently in gene regulation. These proteins are commonly misregulated in different cancers, including GBMs. This bachelor’s thesis is a literature review, which aims to discuss the role of PcG proteins in cancer development and maintenance with a focus on GBMs. In addition, this thesis explains the current knowledge of the structure and function of PRCs and their subunits as repressive epigenetic factors. The current understanding of the role of PRCs in epigenetic regulation covers the basic interactions of the involving proteins. However, the multiple intricate pathways through which PcG proteins interact and function as regulatory elements are not well understood. The key role of PcG proteins in controlling gene expression and the presence of their expressional abnormalities in GBMs makes them potential novel therapeutic targets. Additionally, it is important to gain a better understanding what effects the artificial altering of PcG protein functions has. For example, currently tested PcG inhibitors must be tested for their short- and long-term effects on patients. Overall, more research on the interactions and functions of PcG proteins is needed to better understand the multiple ways their expressional changes can affect GBM progression. Furthermore, the therapeutic methods involving PcGs currently in testing must be further examined for long term effects, such as adverse tumor response. Given time, the usage of PcG proteins as therapeutical targets might bring novel therapies for the treatment of GBMs improving the currently poor diagnosis of the disease