Colorectal cancer prognosis. DNA methylation and microRNA levels predict cancer survival. 6
How epigenetic changes can predict cancer prognosis? How micro RNA can help select personalized therapy for colorectal cancer? DNA methylation in colon cancer progression and treatment. Dr. C. Richard Boland, MD. The second big advance in cancer epigenetics was recognizing that some of the non-coding RNAs in our nucleus make these very short RNA molecules called microRNAs. MicroRNAs get transcribed and processed down to about 20-base segment, which forms into a hairpin. And the feet of the hairpin can interact with the 3-prime untranslated region of messenger RNA. This interaction leads to degradation of messenger RNA. That is a big part of regulating the expression of messenger RNAs. We spend a lot of time understanding what turns ON messenger RNAs. But once messenger RNAs are “ON”, there has to be a way to turn them “OFF”. This is how cell regulates its different metabolic processes. And one of the big parts of this regulation is microRNA expression. The interesting thing about microRNAs is this: There is a complementary recognition between the feet on the microRNA and the 3-prime untranslated region of a messenger RNA. But one microRNA can interact with dozens or maybe a hundred or more of messenger RNAs. So the turning ON or OFF of a microRNA can help orchestrate the expression of lots and lots of genes. It turns out that cancers often have specific patterns of micro RNA expression. That helps us understand a little bit more about the behavior of cancer cells. So microRNAs can also regulate the response to certain treatments Also the methylation of DNA is not permanent. You have discovered in your research that DNA methylation is a process that can be influenced. Yes! That’s a really good point. Dr. C. Richard Boland, MD. Specifically, if you get a mutation or deletion of a gene it’s very hard to reverse it. If there is a specific point mutation, the likelihood that you’ll get another strike at that very spot and correct the error is too small to be imagined. Likewise, the deletion of a gene is permanent. There are mechanisms, whereby there could be a gene duplication, and you can replace a missing gene. But those are unlikely to occur. DNA methylation is different. We know that some colon cancers are driven by excess DNA methylation. But that methylation is reversible: DNA methyltransferase puts the methyl groups on, but there are demethylation enzymes that can take them off. DNA methylation process can be manipulated. So the intriguing part about DNA methylation is you can reverse it too. We have medications in the laboratory that can turn DNA methylation off. Some of those medications have been used in people. They are toxic but they can be used. Now people are thinking about medications or even foods or naturally occurring compounds that can manipulate DNA methylation. If we can find a compound that can safely alter DNA methylation process in a predictable way. That would be really great. Dr. Anton Titov, MD. That’s a very interesting, exciting and important direction of research. Potentially even dietary regulation of methylation is possible. It will be important not only for colorectal cancer but for other types of cancers too. Yes, definitely!
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