RNA and cancer
The researchers told how RNA affects the development of oncopathology
An international group of scientists and physicians with the participation of researchers from the Higher School of Economics studied the effect of microRNAs and long non-coding RNAs on the development of ovarian cancer in women. Scientists examined more than a hundred tumor samples and found out that certain microRNAs prevent cell mutation, and long non-coding RNAs binding them, on the contrary, stimulate it. The results obtained may help in the development of a new type of pharmaceutical drugs that regulate microRNA concentrations in patients. The study was published in the International Journal of Molecular Sciences (Loginov et al., Aberrant Methylation of 20 miRNA Genes Specifically Involved in Various Steps of Ovarian Carcinoma Spread: From Primary Tumors to Peritoneal Macroscopic Metastases).
DNA and RNA provide the work of our organisms. DNA stores and transmits genetic data for generations, serves as an instruction for cell development. RNA copies DNA and participates in the synthesis of specialized RNAs or proteins necessary for life. But there are also non-coding RNAs that are never "translated" into proteins, but participate in molecular processes, perform transport and regulatory functions.
Depending on the structure and sequence of nucleotides, regulatory RNAs can hinder or, conversely, contribute to the development of oncological diseases. One of them is ovarian cancer, the most aggressive tumor among malignant neoplasms, which ranks first in the world in terms of the number of deaths.
A team of scientists with the participation of researchers from the HSE International Bioinformatics Laboratory studied the role of RNA in the development of ovarian cancer. The researchers analyzed the characteristics of the patients' tissues at different stages: early and later, when metastases had already appeared. A total of 102 tumor samples and a control group of 102 healthy tissues of the same patients were studied.
All tissues and organs of the body are covered with epithelial cells. Normally, these cells are immobile, closely connected to each other and a special basement membrane. But when these cells become tumorous, they change their structure and functions. This process is called epithelial-mesenchymal transition: under external influence, the cell changes its type and turns into mesenchymal.
Its shell becomes thinner, its shape elongated. The cells lose their connection with each other and the basement membrane, become mobile and penetrate into the bloodstream. The separated tumor cells are transferred by the blood or lymph flow to other organs and form metastases, which is why the cancer progresses.
Scientists have found out how RNA molecules affect the epithelial-mesenchymal transition. microRNAs act as an oncoprotector. They attach to matrix RNAs synthesizing "dangerous" proteins and block their work. Thus, they protect cells from this transition, slow down the course of the disease.
And long non-coding RNAs, on the contrary, aggravate the disease. They intercept microRNAs and interfere with their work, which is why the synthesis of proteins that stimulate cell changes occurs in the same volume. The body's defense is reduced, and the risk of metastasis formation becomes higher.
The study also showed that specific methyl groups on non-coding DNA sites can completely block the synthesis of protective microRNAs. Methylation is one of the main mechanisms for suppressing gene activity. To "turn off" the gene, a small molecule, a methyl group, binds to it, after which protective RNAs are not formed at all.
The researchers emphasize that DNA methyl groups can both be transmitted through the maternal line and formed during life, and randomly. Now only the theory of this process is being investigated. Scientists cannot influence the methyl groups of DNA yet: the structure is too stable.
"microRNAs are now a popular research topic. Coding RNAs have been studied well, but there is still not enough research on their regulation, and discussions are going on in the scientific community," comments one of the authors of the article, a researcher HSE International Bioinformatics Laboratory Olga Brovkina. — We have studied in detail the regulatory elements that affect the epithelial-mesenchymal transition, and have checked the results several times. I hope they will be able to help in the development of a new type of pharmaceutical drugs aimed at regulating microRNA concentrations in patients."
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