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Analysis of somatic mutations in miRNA biogenesis genes

The creation by Polish scientists of an atlas of somatic mutations in genes of proteins involved in the formation and function of miRNAs is a breakthrough in the field of cancer genetics.

Cancer development is associated with the accumulation of a number of somatic mutations within the cell’s genetic material (DNA).

Somatic mutations are found in the majority of tumor cells and are referred to as acquired, or non-hereditary, changes. These mutations condition the uncontrolled multiplication of tumor cells which results in clonal expansion leading to tumor growth. Some of the functional somatic mutations in the cancer genome cause loss of function of suppressor genes (i.e. genes whose task is to inhibit the processes of cell growth and differentiation and to maintain the genetic stability of the cell), while others are of an activating nature, leading to the acquisition of new functions and activation of oncogenes.

Identification of these functional mutations allows better understanding of the processes occurring in tumors and becomes the basis for the development of new markers or personalized cancer therapies.

Scientists from the Institute of Bioorganic Chemistry of the Polish Academy of Sciences (IPC PAS), in collaboration with Professor Piotr Kozłowski, presented the first comprehensive analysis (atlas) of somatic mutations in genes of proteins involved in the formation and function of miRNAs. The researchers also showed what is the effect of these mutations on the level of microRNAs in the cancer cell. In some cases, they also indicated the clinical effects of such mutations, including showing their impact on a patient’s chances of survival.

MicroRNAs (miRNAs) are short, non-coding, single-stranded RNA molecules (about 21 nucleotides long) that play important roles in the post-transcriptional regulation of most protein-coding genes. It can be said that microRNAs are “gatekeepers” taking care of the proper course of processes in the cell.

Expression of more than 30% of human genes is controlled by miRNAs. Although the biological function of most of the microRNAs identified so far is still unknown, it has been shown that miRNA molecules affect the down-regulation of gene expression, as well as participate in the stimulation or inhibition of many important biological processes and pathogenic processes, including tumorigenesis. The role of miRNAs in tumorigenesis has recently become an object of interest for many researchers, which allowed the identification of a number of miRNAs involved in oncogenesis.

The subject of research conducted at the Institute of Bioorganic Chemistry of the PAS was primarily the analysis of miRNA expression. Polish scientists have analyzed the occurrence of somatic mutations in a panel of 29 genes involved in the biogenesis and function of miRNAs. For this purpose, they used data from more than 10 thousand samples of various types of cancer, collected in a repository The Cancer Genome Atlas (TCGA). Scientists from Poznan identified more than 3600 somatic mutations and detected genes enriched in mutations in specific types of cancer. As a result of their analysis, the researchers also identified a number of recurrent hotspot mutations and demonstrated that the occurrence of hotspot mutations in genes such as SMAD4, SMAD2 or DICER1 affects microRNA biogenesis and correlates with altered miRNA expression levels and reduced patient survival.

This work is a great contribution to the development of cancer genetics and the results obtained extend the knowledge of mutations occurring in individual cancers.

These findings are described in the article entitled „A pan-cancer atlas of somatic mutations in miRNA biogenesis genes” published in the journal Nucleic Acids Research, 06.01.2021(Authors: Galka-Marciniak P., Urbanek-Trzeciak M., Nawrocka P., Kozlowski P.), DOI: 10.1093/nar/gkaa1223
Translation was done with the assistance of DeepL translator.