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World J Hematol. May 6, 2016; 5(2): 51-60
Published online May 6, 2016. doi: 10.5315/wjh.v5.i2.51
Role of microRNA in regulation of myeloma-related angiogenesis and survival
Michal A Rahat, Meir Preis
Michal A Rahat, Immunology Research Unit, Carmel Medical Center, Haifa 3436212, Israel
Michal A Rahat, Ruth and Bruce Rappaport Faculty of Medicine, Technion, Haifa 3109601, Israel
Meir Preis, Institute of Hematology, Carmel Medical Center, Haifa 3436212, Israel
Author contributions: Both authors contributed equally to the concept of the paper, the writing of the manuscript and its critical revisions, and for its final approval.
Supported by The Israel Cancer Association, No. 20150048.
Conflict-of-interest statement: The authors have no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Michal A Rahat, DSc, Assistant Professor, Immunology Research Unit, Carmel Medical Center, 7 Michal St., Haifa 3436212, Israel. rahat_miki@clalit.org.il
Telephone: +972-4-8250404 Fax: +972-4-8250408
Received: August 13, 2015
Peer-review started: August 13, 2015
First decision: November 6, 2015
Revised: November 19, 2015
Accepted: January 21, 2016
Article in press: January 22, 2016
Published online: May 6, 2016
Processing time: 259 Days and 1.2 Hours
Abstract

Multiple myeloma (MM) is a malignant disease caused by clonal proliferation of plasma cells that result in monoclonal gammopathy and severe end organ damage. Despite the uniform clinical signs, the disease is very diverse in terms of the nature and sequence of the underlying molecular events. Multiple cellular processes are involved in helping the malignant cells to remain viable and maintain proliferative properties in the hypoxic microenvironment of the bone marrow. Specifically, the process of angiogenesis, triggered by the interactions between the malignant MM cells and the stroma cells around them, was found to be critical for MM progression. In this review we highlight the current understanding about the epigenetic regulation of the proliferation and apoptosis of MM cells and its dependency on angiogenesis in the bone marrow that is carried out by different microRNAs.

Keywords: Multiple myeloma; MicroRNA; Angiogenesis; Proliferation; Apoptosis; Hypoxia; Vascular endothelial growth factor; Hypoxia-induce factor 1α; Macrophages; Endothelial cells

Core tip: The pathogenesis of multiple myeloma (MM) requires that malignant cells remain viable and proliferate. Therefore, genes relating to the regulation of apoptosis, proliferation and angiogenesis are tightly regulated. Specifically, angiogenesis, which is driven by the interactions between the malignant cells and stroma cell surrounding them, is critical for MM progression. In this review we summarize the current knowledge about the regulation of the expression of genes related to apoptosis, proliferation and angiogenesis, through the activity of specific microRNAs.