J 2017

Alternative mechanisms of miR-34a regulation in cancer

SLABÁKOVÁ, Eva, Z. CULIG, Ján REMŠÍK and Karel SOUČEK

Basic information

Original name

Alternative mechanisms of miR-34a regulation in cancer

Authors

SLABÁKOVÁ, Eva (203 Czech Republic), Z. CULIG (40 Austria), Ján REMŠÍK (703 Slovakia, belonging to the institution) and Karel SOUČEK (203 Czech Republic, guarantor, belonging to the institution)

Edition

CELL DEATH & DISEASE, LONDON, NATURE PUBLISHING GROUP, 2017, 2041-4889

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 5.638

RIV identification code

RIV/00216224:14310/17:00100427

Organization unit

Faculty of Science

UT WoS

000414022900059

Keywords in English

EPITHELIAL-MESENCHYMAL TRANSITION; CHRONIC LYMPHOCYTIC-LEUKEMIA; TUMOR-SUPPRESSOR; PROSTATE-CANCER; MICROPROCESSOR COMPLEX; HEPATOCELLULAR-CARCINOMA; NEUROBLASTOMA-CELLS; MICRORNA EXPRESSION; MOTILE CILIOGENESIS; MIRNA BIOGENESIS

Tags

Tags

International impact, Reviewed
Změněno: 28/3/2018 13:26, Ing. Nicole Zrilić

Abstract

V originále

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.