Implication of microRNAs in Carcinogenesis with Emphasis on Hematological Malignancies and Clinical Translation

Abstract

MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs, that are involved in the multistep process of carcinogenesis, contributing to all established hallmarks of cancer. In this review, implications of miRNAs in hematological malignancies and their clinical utilization fields are discussed. As components of the complex regulatory network of gene expression, influenced by the tissue microenvironment and epigenetic modifiers, miRNAs are “micromanagers” of all physiological processes including the regulation of hematopoiesis and metabolic pathways. Dysregulated miRNA expression levels contribute to both the initiation and progression of acute leukemias, the metabolic reprogramming of malignantly transformed hematopoietic precursors, and to the development of chemoresistance. Since they are highly stable and can be easily quantified in body fluids and tissue specimens, miRNAs are promising biomarkers for the early detection of hematological malignancies. Besides novel opportunities for differential diagnosis, miRNAs can contribute to advanced chemoresistance prediction and prognostic stratification of acute leukemias. Synthetic oligonucleotides and delivery vehicles aim the therapeutic modulation of miRNA expression levels. However, major challenges such as efficient delivery to specific locations, differences of miRNA expression patterns between pediatric and adult hematological malignancies, and potential side effects of miRNA-based therapies should be considered.

miR-1202 acts as anti-oncomiR in myeloid leukaemia by down-modulating GATA-1 S expression

“…miRNAs are widely involved in the regulation of processes such as apoptosis, cell differentiation and cell proliferation thus suppressing or promoting the progression of human cancers. In the context of leukaemogenesis, different miRNAs have emerged as important regulators of haematopoiesis [52][53][54]. Based on these observations, it has been proposed that dysregulated miRNA-mediated gene expression might cooperate with GATA-1 S in promoting pre-leukaemia in DS or contribute to control GATA-1 expression levels [21,24].…”

MiR-130a-3p regulates FUNDC1-mediated mitophagy by targeting GJA1 in myocardial ischemia/reperfusion injury

“…miRNAs play an important role in the pathogenesis and prognosis of cardiac diseases, and can also be an important therapeutic target [ 7 ]. MiRNAs are a class of short and highly conserved non-coding RNAs [ 8 ]. Increasing pieces of evidence have suggested that miRNAs are involved in the occurrence and development of heart disease by regulating the mitochondria-related genes, including biogenesis, fission, and mitophagy genes [ 9 , 10 ].…”

MiR-130a-3p Regulates FUNDC1-Mediated Mitophagy by Targeting GJA1 in Myocardial Ischemia/Reperfusion Injury

“…MiRNAs are a class of short and highly conserved non-coding RNAs (8). Increasing pieces of evidence have suggested that miRNAs are involved in the occurrence and development of heart disease by regulating the mitochondria-related genes, including biogenesis, ssion, and mitophagy genes (9,10).…”