An international group of scientists and doctors, with the participation of researchers from the National Research University Higher School of Economics, studied the effect of miRNAs and long non-coding RNAs on the development of ovarian cancer in women. The scientists examined more than a hundred tumor samples and found that certain microRNAs prevent cell mutation, while the long non-coding RNAs that link them, on the contrary, stimulate it. The results obtained may help in the development of a new type of pharmaceutical products that regulate microRNA concentrations in patients. to study
DNA and RNA make our organisms work. DNA stores and transmits genetic data for generations, serving as instructions for cell development. RNA makes copies of DNA and is involved in the synthesis of specialized RNA or proteins necessary for life. But there are also non-coding RNAs that are never “translated” into proteins, but instead participate in molecular processes and perform transport and regulatory functions.
Depending on the structure and sequence of the nucleotides, regulatory RNAs can prevent or, on the contrary, promote 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 number of deaths.
A team of scientists, including 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 from the same patients were studied.
All tissues and organs of the body are covered with epithelial cells. Normally, these cells are immobile, tightly connected to each other and with a special basement membrane. But when these cells become cancerous, they change their structure and function. This process is called epithelial-mesenchymal transition: under external influence, the cell changes type and becomes mesenchymal.
Its shell becomes thinner, the shape is elongated. The cells lose contact with each other and with the basement membrane, become motile and enter the bloodstream. Separated tumor cells are carried by the blood or lymph to other organs and form metastases, so the cancer progresses.
Scientists have discovered how RNA molecules affect the epithelial-mesenchymal transition. MicroRNAs act as oncoprotectors. They join the messenger RNA by synthesizing “dangerous” proteins and block its work. Thus, they protect the cells from this transition, slow down the course of the disease.
And long non-coding RNA, on the contrary, aggravates the disease. They intercept miRNAs and interfere with their work, so the synthesis of proteins that stimulate cellular changes occurs in the same volume. The body’s defenses are reduced and the risk of metastasis formation is greater.
The study also showed that specific methyl groups in non-coding DNA regions can completely block the synthesis of protective miRNAs. Methylation is one of the main mechanisms of gene suppression. To “turn off” a gene, a small molecule, a methyl group, is attached to it, after which no protective RNAs are formed.
The researchers emphasize that DNA methyl groups can be passed on through the maternal line or formed during life, and in a random way. Currently only the theory of this process is being investigated. Scientists cannot yet influence the methyl groups of DNA: the structure is too stable.
“MicroRNA is now a popular research topic. Coding RNAs have been well studied, but studies of their regulation are still insufficient and there are discussions in the scientific community,” comments Olga Brovkina, one of the authors of the article, a researcher at the International Laboratory of Bioinformatics HSE. “We studied in detail the regulatory elements that influence the epithelial-mesenchymal transition and checked the results several times. I hope they can help in the development of a new type of pharmaceuticals aimed at regulating microRNA concentrations in patients.”
HSE Press Office