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@article{1411856, author = {Slabáková, Eva and Culig, Z. and Remšík, Ján and Souček, Karel}, article_location = {LONDON}, article_number = {October}, doi = {http://dx.doi.org/10.1038/cddis.2017.495}, keywords = {EPITHELIAL-MESENCHYMAL TRANSITION; CHRONIC LYMPHOCYTIC-LEUKEMIA; TUMOR-SUPPRESSOR; PROSTATE-CANCER; MICROPROCESSOR COMPLEX; HEPATOCELLULAR-CARCINOMA; NEUROBLASTOMA-CELLS; MICRORNA EXPRESSION; MOTILE CILIOGENESIS; MIRNA BIOGENESIS}, language = {eng}, issn = {2041-4889}, journal = {CELL DEATH & DISEASE}, title = {Alternative mechanisms of miR-34a regulation in cancer}, volume = {8}, year = {2017} }
TY - JOUR ID - 1411856 AU - Slabáková, Eva - Culig, Z. - Remšík, Ján - Souček, Karel PY - 2017 TI - Alternative mechanisms of miR-34a regulation in cancer JF - CELL DEATH & DISEASE VL - 8 IS - October SP - 1-10 EP - 1-10 PB - NATURE PUBLISHING GROUP SN - 20414889 KW - EPITHELIAL-MESENCHYMAL TRANSITION KW - CHRONIC LYMPHOCYTIC-LEUKEMIA KW - TUMOR-SUPPRESSOR KW - PROSTATE-CANCER KW - MICROPROCESSOR COMPLEX KW - HEPATOCELLULAR-CARCINOMA KW - NEUROBLASTOMA-CELLS KW - MICRORNA EXPRESSION KW - MOTILE CILIOGENESIS KW - MIRNA BIOGENESIS N2 - MicroRNA miR-34a is recognized as a master regulator of tumor suppression. The strategy of miR-34a replacement has been investigated in clinical trials as the first attempt of miRNA application in cancer treatment. However, emerging outcomes promote the re-evaluation of existing knowledge and urge the need for better understanding the complex biological role of miR-34a. The targets of miR-34a encompass numerous regulators of cancer cell proliferation, survival and resistance to therapy. MiR-34a expression is transcriptionally controlled by p53, a crucial tumor suppressor pathway, often disrupted in cancer. Moreover, miR-34a abundance is fine-tuned by context-dependent feedback loops. The function and effects of exogenously delivered or re-expressed miR-34a on the background of defective p53 therefore remain prominent issues in miR-34a based therapy. In this work, we review p53-independent mechanisms regulating the expression of miR-34a. Aside from molecules directly interacting with MIR34A promoter, processes affecting epigenetic regulation and miRNA maturation are discussed. Multiple mechanisms operate in the context of cancer-associated phenomena, such as aberrant oncogene signaling, EMTor inflammation. Since p53-dependent tumor-suppressive mechanisms are disturbed in a substantial proportion of malignancies, we summarize the effects of miR-34a modulation in cell and animal models in the clinically relevant context of disrupted or insufficient p53 function. ER -
SLABÁKOVÁ, Eva, Z. CULIG, Ján REMŠÍK and Karel SOUČEK. Alternative mechanisms of miR-34a regulation in cancer. \textit{CELL DEATH \&{} DISEASE}. LONDON: NATURE PUBLISHING GROUP, 2017, vol.~8, October, p.~1-10. ISSN~2041-4889. Available from: https://dx.doi.org/10.1038/cddis.2017.495.
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