Informace o publikaci
Alternative mechanisms of miR-34a regulation in cancer
| Autoři | |
|---|---|
| Rok publikování | 2017 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | CELL DEATH & DISEASE |
| Fakulta / Pracoviště MU | |
| Citace | |
| Doi | http://dx.doi.org/10.1038/cddis.2017.495 |
| Klíčová slova | EPITHELIAL-MESENCHYMAL TRANSITION; CHRONIC LYMPHOCYTIC-LEUKEMIA; TUMOR-SUPPRESSOR; PROSTATE-CANCER; MICROPROCESSOR COMPLEX; HEPATOCELLULAR-CARCINOMA; NEUROBLASTOMA-CELLS; MICRORNA EXPRESSION; MOTILE CILIOGENESIS; MIRNA BIOGENESIS |
| Popis | 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. |