Role of tumor suppressor p53 and micro-RNA interplay in multiple myeloma pathogenesis

The molecular mechanisms underlying dysregulated wild type (wt) p53 in multiple myeloma (MM) have been subjects of intense investigation for years. Indeed, correlation of rarely occurring TP53 gene mutations or deletions with adverse clinical outcomes in MM patients is strongly established, while in...

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Bibliographic Details
Published in:Journal of hematology and oncology Vol. 10; no. 1; pp. 169 - 11
Main Authors: Abdi, Jahangir, Rastgoo, Nasrin, Li, Lihong, Chen, Wenming, Chang, Hong
Format: Journal Article
Language:English
Published: London BioMed Central 26.10.2017
BioMed Central Ltd
Springer Nature B.V
BMC
Subjects:
Apoptosis
Cancer
Cancer Research
Causes of
Cell cycle
Development and progression
Disease resistance
Drug resistance
Exploration
Gene expression
Genetic aspects
Hematology
Humans
Leukemia
Medicine
Medicine & Public Health
Micro-RNA
MicroRNA
MicroRNAs - metabolism
miRNA
Molecular modelling
Multiple myeloma
Multiple Myeloma - genetics
Multiple Myeloma - metabolism
Multiple Myeloma - pathology
Mutation
Myeloma
Oncology
p53
p53 Protein
Pathogenesis
Physiological aspects
Regulatory sequences
Review
Tumor suppressor genes
Tumor Suppressor Protein p53 - metabolism
Canada
Micro-RNA
Myeloma
p53
ISSN:1756-8722, 1756-8722
Online Access:Get full text
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Summary:The molecular mechanisms underlying dysregulated wild type (wt) p53 in multiple myeloma (MM) have been subjects of intense investigation for years. Indeed, correlation of rarely occurring TP53 gene mutations or deletions with adverse clinical outcomes in MM patients is strongly established, while in majority of cases wtp53 seems to be non-functional or dysregulated bearing a high clinical impact. Interestingly, findings from recent investigations show that micro-RNAs (miRNAs) may contribute to suppression of wtp53 in MM, as they are now known to function as key regulatory elements in the p53 network. This area is shedding new light on understanding the biologic effects of dysregulated p53 in MM pathogenesis especially drug resistance. miRNAs such as miR-125b (oncomiR) or miR-34a (tumor suppressor-miR) can be negative or positive regulators of wtp53 function, respectively, with specific effects on MM cell viability. On the other hand, our knowledge of miRNA interaction with mutant (mt) p53 in MM, which is rather related to disease progression and resistance to therapy, is limited which demands in-depth exploration. Here, we will put forward the current knowledge on miRNA-p53 interaction in MM and its role in MM pathogenesis including drug resistance. We will also highlight the pre-clinical approaches for therapeutic application of miRNAs targeting p53 pathway.
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ISSN:1756-8722
1756-8722
DOI:10.1186/s13045-017-0538-4