Chronic inflammation because of infection or conditions like chronic inflammatory bowel disease is seemingly linked with around 25 percent of all cancers. In an attempt to point out the exact way inflammation triggers cancer, experts from the Ohio State University Comprehensive Cancer Center have now found that inflammation stimulates an increase in levels of a molecule named microRNA-155 (miR-155). A raise in the level of this molecule in turn, supposedly drops levels of proteins involved in DNA repair, resulting in a higher rate of spontaneous gene mutations, which can lead to cancer.
MicroRNAs appear as a large family of non-coding genes involved in many important cell processes. These genes allegedly carry out this function by suppressing the amount of particular proteins in cells, with each type of microRNA often affecting many different proteins. The MiR-155 is believed to influence blood-cell maturation, immune responses and autoimmune disorders. High levels of this molecule are possibly related to the development of leukemias, as well as breast, lung and gastric cancers.
“Our study shows that miR-155 is upregulated by inflammatory stimuli and that overexpression of miR-155 increases the spontaneous mutation rate, which can contribute to tumorigenesis. People have suspected for some time that inflammation plays an important role in cancer, and our study presents a molecular mechanism that explains how it happens. Our findings also suggest that drugs designed to reduce miR-155 levels might improve the treatment of inflammation-related cancers,” quoted first investigator and post-doctoral researcher Dr. Esmerina Tili.
As a part of the research, investigators inspected the apparent effects of inflammation-promoting substances such as tumor necrosis factor or lipopolysaccharide on miR-155 expression. Experts also examined the frequency of spontaneous mutations in several breast-cancer cell lines. When breast-cancer cells were exposed to the two inflammatory factors, the levels of miR-155 probably elevated abnormally high, and the mutation rate raised two- to three-fold. In order to figure out the precise reason behind this, researchers aimed to understand the WEE1 gene, which stops the process of cell division for allowing damaged DNA to be repaired.
It was pointed out that miR-155 may also target WEE1 and high levels of miR-155 can cause a drop in the levels of WEE1. Low levels of WEE1 purportedly enabled cell division to continue even when DNA damage is present, leading to a growing number of mutations. On completion of the study, it was asserted that miR-155, which is associated with inflammation, raises the mutation rate and is a hallmark in inflammation-induced cancers. This may serve as a vital therapeutic target in the near future as well.
The research was published recently in the Proceedings of the National Academy of Sciences.