Experimenting with the laboratory of brain cancer cells, researchers at Johns Hopkins Medicine have added evidence that the lack of specific tiny molecules that dampen certain genes associated with the development and growth of brain tumors in children, known as low-grade gliomas.
Report on the results was published in the autumn of 2018 in the "scientific reports" and supports the idea of increasing the levels of microRNAs as a potential treatment for these tumors.
Approximately 1,600 cases of low-grade gliomas (PLGG) are diagnosed annually in the United States in children, and the vast majority of these slow-growing tumors can be treated and cured, mainly by surgical removal, although in some cases, surgery may damage the adjacent brain tissue, depending the location of the tumor. In contrast to the high-grade glioblastomas, such as the one that claimed the life of Sen. John McCain of Arizona, PLGG mainly affects school-age children and young people.
"It has long been known that microRNAs play a role in the fight against various tumor characteristics, such as growth," - says Fausto Rodriguez, Ph.D., an associate professor at the University of John Hopkins School of Medicine pathology and senior author of the study.
"Our results revealed a subset of microRNAs, which in sufficient quantities, appears to reduce the growth and invasion of cancer cells in low-grade gliomas in children."
MicroRNAs are tiny molecules that control the entire gene networks that provide proteins substantially do not give them responsible for the regulation of biological processes, such as nutrient uptake, cell growth and cell death. Altered levels of specific miRNAs can disrupt the entire biological pathways because erroneous portion genes can upset the entire network.
"One miRNA can aim for several genes and has a profound impact on cellular processes and changing dynamic", - said Rodriguez, who says that PLGG are good candidates for the analysis of types and miRNA levels as genetically PLGG stable compared with other tumors. According to him, this is relatively easy to identify any relevant genetic abnormalities and potential targets for therapy.
For the new study, the researchers first analyzed previously collected data subtype microRNA in two studies. They studied tumors in 125 patients with low-grade gliomas for the levels of specific miRNA known as miR-125b, using chromogenic hybridization in situ (CISH), which is applicable to tissue being treated commonly in pathology and allows identification of specific miRNAs in cells of interest. Levels of miRNA were below 43 pilocytic astrocytomas (the most abundant subtype PLGG) compared to 24 diffuse astrocytomas and normal brain tissues.
Then, Rodriguez and the research team reviewed eight cancer cell lines derived from brain (glial) tumors in children for levels of microRNA 125b-p, using a method that can quickly make thousands to millions of copies of the gene sequence for easier analysis. Although 125b-p microRNA levels varied depending on cell lines grown in the laboratory, they are fairly and uniformly decreased in cancer cell lines than cancer cells, according to Rodriguez.
In further experiments, aimed at defining the role of miRNA in cell growth, researchers have increased levels of miR-125b in the cancer cell lines by introducing the DNA segments in tumor cells using specific viruses and observed a decrease in cell division and growth. , Which indicates that the increase in the level of microRNA 125b may stop the growth of PLGG to check whether cell death contributed to a decrease in cell growth, painted Rodriguez cells containing high levels of microRNA 125b, cell death observed in all cell lines.
"This discovery is an example of how advances in precision medicine can show how increasing levels of specific genes and miRNAs could be targeted for treatment PLGG», - says Rodriguez.