The latest paper of Dr. Jazdzewski’s team regarding the microRNA expression and sequence profiles in hepatic tissue and their aberrances in cirrhosis and hepatocellular carcinoma.
Liver malignancies, including hepatocellular carcinoma (HCC) are the third cause of death from cancer worldwide. Molecular changes underlying tumorigenic changes in hepatic cells are largly unknown and potentially result from aberrant expression of microRNAs.
The discovery of microRNAs, non-coding regulators of gene expression, was a milestone in the quest to understand the pathogenesis of numerous human diseases. Aberrances in microRNA expression or sequences lead to deregulation of numerous genes and pathways.
Recent studies proved that the world of microRNAs is significantly more complex than it was expected. An individual miRNA gene may give rise to several mature miRNAs of varying length, named isomiRs, whose sequence variations lead to changes of the miR’s seed region and, in consequence, to recognition and regulation of distinct sets of target genes.
To reveal the complete microcosm of liver, we analyzed microRNA expression in 24 pairs of hepatocellular carcinoma and adjacent, non-tumorous tissue, including 15 tissues with cirrhosis, using next-generation sequencing. As a result, we obtained expression profiles of canonical microRNAs and their newly identified isoforms whose aberrances potentially underlie initiation and progression of liver cirrhosis and carcinogenesis. Over 30% of seed sequences of the most deregulated microRNA isoforms differ from the canonical seed sequences deposited in miRBase, and consequently regulate the expression of different target genes. Our study gives a solid basis for the understanding of the miR-mediated pathways of carcinogenesis and for the future work on the microRNA-mediated regulation of gene expression in liver. Tissue-specific microRNA profiles can be further used for elaboration of molecular tools for diagnostics and therapies of liver cancer.
The authors of the paper: Anna Wojcicka, Michal Swierniak, Oskar Kornasiewicz, Wojciech Gierlikowski, Monika Maciag, Monika Kolanowska, Marta Kotlarek, Barbara Gornicka, Lukasz Koperski, Grzegorz Niewinski, Marek Krawczyk and Krystian Jazdzewski