Hypoxia is the key regulatory factor of cancer epigenetics

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biokit
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Hypoxia is the key regulatory factor of cancer epigenetics

Post by biokit » Mon Aug 22, 2016 8:33 am

Oxygen is the key factor affecting gene expression, and a regulatory approach which is better understood is called hypoxia inducible factor: when lacking for oxygen, the levels of these transcription factors in many cells increase, and the expression of many hypoxia-related genes is started. Recently, scholars have found another gene regulatory approach of hypoxia: that is, hypoxia can lead to gene methylation, while the hypermethylation may promote proliferation of tumor cells. There are also some recombinant proteins in the market to regulate hypoxia.

DNA methylation can silence gene expression and is a kind of epigenetic regulation which has gone through full and comparative study. DNA methylation can lead to chromatin structure, DNA conformation, DNA stability and the change of way of DNA and protein interactions, thus inhibiting gene expression. Latest studies show that tumor cell hypoxia causes insufficient activity of cell gene demethylation, which leads to gene methylation, thus interfering with certain tumor suppressor genes and promoting tumor growth. The main findings are achieved by professor Diether Lambrechts and have been published in Nature.

In addition to gene mutation, a growing number of studies have found that even without the mutation, tumors can also occur. It turns out to due to change in the cellular epigenetic level. But until now, regulate epigenetic change signal is still not very clear.

Considering that the inhibition role of DNA methylation on expression tumor suppressor gene is the common performance of many tumors, Professor Lambrechts and others studied the epigenetic regulation way of DNA methylation. Firstly, they analyzed tumor tissues of 3000 patients, uncovering the link between oxygen shortage and tumor growth. The researchers hypothesized: can interfering with the oxygen supply interfere tumor cancer progress? They made use of mice to prove that normal blood supply is sufficient to avoid malignant tumors. Their target molecule is TET protein. Professor Lambrechts found that the regulation of hypoxia to TET protein activity only depends on oxygen partial pressure within the cells and is completely unrelated to TET gene expression, hypoxia inducible factor, hypoxia-related metabolism and regulation of gene expression.

Lambrechts said, "Research shows that these epigenetic changes are caused by hypoxia of the environment in which the tumor. Oxygen is the necessary condition of DNA demethylase. When oxygen is insufficient, demethylation activity decreases, leading to excessive methylation reservation. About half of tumor methylation is due to hypoxia, and it has a wider impact on breast, bladder, colorectal, head and neck, kidney, lung and uterinetumors."

Bernard Thienpont said, "Our new insights can make a huge impact on the treatment of cancer. First, the gene methylation changes may be used to indirectly analyse oxygen supply of tumors before, which is valuable to accurately predict tumor behavior and select the ideal treatment. Next, it brings new hope of existing vascular targeting therapy. It is not only helpful to cancer chemotherapy but also helps to suppress the new variant, which in turn helps to reduce the recurrence of tumor aggressiveness."

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