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Exploring Baltic Sea cyanobacteria for small-molecule inhibitors of microRNA function: a project description

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Cyanobacteria constitute a rich source of biologically active and structurally diverse compounds. The pharmacological potential of these compounds resides among others in their ability to control the proliferation and growth of cancer cell lines and potent disease-causing microbial agents. Despite recent scientific advances, the way these compounds interact with the body’s molecular structure are still unclear and science still has to discover how the cyanobacterial metabolites interact with cell structures and how cells react to them. In this project, we will study yet unexamined cyanobacterial metabolites, especially the compounds which act as chemical ligands for microRNA (miRNA) -binding sites, making them promising regulators (inhibitors) of gene networks that are involved in various diseases. We will first develop a stable cell line that constitutively expresses a unique miRNA reporter system. Then, we will conduct a screen on chemical compounds discovered in Baltic cyanobacteria to identify small molecules with inhibitory activity and specificity to MIR92b-3p, which has a significant impact on liver cell behavior in humans. We assume that a successful MIR92b-3p inhibitor will bind to the precursors of MIR92b-3p miRNA, disabling the action of either of the two processing enzymes involved in the biogenesis of any miRNA in a cell (Drosha or Dicer), thus affecting the MIR92b function. The discoveries made with these inhibitory chemical molecules could provide insight into the role of the MIR92 pathway in liver diseases and cancer, and possibly, if promising results appear, they may facilitate a strategy for treating some human diseases in the future.
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Bibliogr. 10 poz., rys.
  • Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, Słoneczna 45G, 10-709 Olsztyn, Poland; Phone +48 895234187; Fax: +48 89 5234131,
  • Faculty of Oceanology and Geography, University of Gdańsk, Gdańsk, Poland
  • Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology, Warsaw, Poland
  • Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, Poland
  • Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, Poland
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  • Brzuzan, P., Florczyk M,, Łakomiak A., Woźny M., 2016. Illumina Sequencing Reveals Aberrant Expression of MicroRNAs and Their Variants in Whitefish (Coregonus lavaretus) Liver after Exposure to Microcystin-LR. PLoS ONE 11(7), e0158899.
  • Childs-Disney, J.L., Disney, M.D. 2016. Approaches to Validate and Manipulate RNA Targets with Small Molecules in Cells. Annual Review of Pharmacology and Toxicology 56, 123-140.
  • Felczykowska, A., Pawlik, A., Mazur-Marzec, H., ToruńskaSitarz, A., Narajczyk, M., Richert, M., Węgrzyn, G., Herman-Antosiewicz, A. 2015. Selective inhibition of cancer cells' proliferation by compounds included in extracts from Baltic Sea cyanobacteria. Toxicon 108, 1-10.
  • Häggqvist, K., Torunska-Sitarz, A., Błaszczyk, A., MazurMarzec, H., Meriluoto, J. 2016. Morphologic, phylogenetic and chemical characterization of a brackish colonial picocyanobacterium (Coelosphaeriaceae) with bioactive properties. Toxins 8, 108, 2-17.
  • Hata, A., Lieberman, J., 2015. Dysregulation of microRNA biogenesis and gene silencing in cancer. Sci Signal 8, re3. doi:10.1126/scisignal.2005825
  • Mazur-Marzec, H., Błaszczyk, A., Felczykowska, A., Hohlfeld, N., Kobos, J., Toruńska–Sitarz, A., Prabha, D., Montalvão, S., D’Souza , L., P. Tammela, P., Mikosik, A., Bloch S., Nejman–Faleńczyk, B., Węgrzyn, G., 2015. Baltic cyanobacteria - a source of biologically active compounds. Eur. J. Phycol., 50, 343-360.
  • Oftedal, L., Selheim F., Wahlsten M., Sivonen K., Doskeland S.O., Herfindal L. 2010. Marine benthic cyanobacteria contain apoptosis-inducing activity synergizing with daunorubicin to kill leukemia cells, but not cardiomyocytes. Mar. Drugs 8, 2659-2672.
  • Spoof, L., Błaszczyk, A., Meriluoto, J., Cegłowska, M., Mazur-Marzec, H. 2016. Structures and Activity of New Anabaenopeptins Produced by Baltic Sea Cyanobacteria. Marine Drugs 2016, 14(1), 8.
  • Zhuang, LK., Yang YT., Ma X., Han B., Wang ZS., Zhao QY., Wu LQ., Qu ZQ., 2016. MicroRNA-92b promotes hepatocellular carcinoma progression by targeting Smad7 and is mediated by long non-coding RNA XIST. Cell Death Dis.7, e2203.
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