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Epigenetic News, How Long Noncoding RNA Can Regulate Colon Cancer

Long Noncoding RNA, Junk DNA, lncRNA

What are Long Noncoding RNAs?

Long Noncoding RNA – A lot of us may remember learning in high school biology that only a very small fraction of the genome actually contains genes; the rest of it is nonfunctioning “junk” DNA. As is common in science, the last 10 years of biological research have proved this hypothesis to be very wrong. The traditional central dogma of biology taught that DNA is a template for making RNA and that RNA is a template for making protein.

However, researchers have recently discovered that a large part of what we once considered to be junk, actually codes for many different types of RNA molecules that don’t make protein and play important roles in regulating cellular functions. One such class of RNA molecules is known as long noncoding RNA (lncRNA). These are large molecules of RNA that exhibit enzymelike functions in the cell. [1]

What is DNA Methylation?

DNA methylation, or the addition of methyl (CH3) groups to base pairs on genes, has long been known as a mechanism for the regulation of gene expression, as well as one of the most prominent types of epigenetic modifications found in mammals. Generally, higher levels of methylation on a specific gene result in lower levels of that gene being expressed. Furthermore, these modifications are particularly important because they can persist throughout the natural cell division of a person’s lifetime, and can even be passed on from parent to child.

Because DNA methylation is a regulator of gene expression, it is very important for understanding the growth of certain types of cancers and tumors. For example, tumors often result from the overexpression of genes that are associated with growth. In some instances, the cause of this can be partially traced to low levels of methylation (hypomethylation) of these genes. This mistake in methylation patterns causes the cell to think that it’s supposed to grow and divide, resulting in a tumor. Of course, cancer is an extremely complicated disease, and there is rarely ever only one cause. However, understanding DNA methylation will undoubtedly lead to a better understanding of tumor growth.

Currently, recent scientific research suggests that long noncoding RNA may be playing an important role in managing DNA methylation patterns. [2]

Long Noncoding RNA has Associations with DNA Methylation and Cancer

Ahmad Khalil, a geneticist at Case Western Reserve University in Ohio, says “No one understands what’s driving the hypomethylation in cancer cells. The initial hypothesis was that maybe the enzymes regulating histone modification or DNA methylation are mutated, or their expression is deregulated.” [3]

Khalil and his team had previously observed that genes, which normally had low expression levels, were significantly upregulated without the presence of lncRNAs that bound to enzymes associated with histone modifications (another type of epigenetic modification). [4]

Using the same line of thought, Khalil theorized that lncRNAs might also play a role in the methylation of DNA. In order to test this theory, the methylation enzyme DNMT1 was isolated from mammalian cells. Any RNA that was bound to DNMT1 was then removed and sequenced. The results revealed that a large number of lncRNAs associate with DNMT1, indicating that they may play an important role in the methylation of DNA.

A later analysis showed that one of those lncRNA’s, called DACOR1, was deregulated in colon cancer. Khali asked, “What happens if we put this lncRNA back into the cancer cells?” When his team tried to re-introduce the lncRNA back to the cell line, they discovered that some DNA methylation was restored, and the growth of cancer colonies was reduced.

Beyond Colon Cancer

This discovery has the potential to lead to not only an increased understanding of cancer but also the complexity of the mechanisms of epigenetic modification on a genome-wide scale. Furthermore, the use of lncRNA in new therapeutics is an undeniable possibility for the future of medicine. The role that lncRNA plays in methylation has yet to be elucidated, and continued research will undoubtedly yield exciting findings that will further our understanding of epigenetics and many other cellular processes.

References:

[1] https://www.theguardian.com/science/2012/sep/05/genes-genome-junk-dna-encode
[1] http://healthland.time.com/2012/09/06/junk-dna-not-so-useless-after-all/

[2]
 http://hmg.oxfordjournals.org/content/24/21/6240.abstract
[3] http://www.the-scientist.com//?articles.view/articleNo/44833/title/Managing-Methylation/
[4] https://conceptualrevolutions.com/2016/01/24/rna-modifications-mapped-major-epigenetic-breakthrough/ 

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    By: Nicholas Morano

    Nicholas Morano received his B.S. in biochemistry from Binghamton University, where he worked as an undergraduate researcher studying the genetics of drosophila melanogaster. He is currently working on his PhD. in biochemistry at Albert Einstein’s College of Medicine, where he is studying nucleic acids for the purpose of developing new technologies and new therapeutics.

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