Investigation of microRNA alterations in leukemias and lymphomas

Abstract

Alterations in miRNA genes play a critical role in the pathophysiology of many, perhaps all, human cancers: cancer initiation and progression can involve alterations of microRNA genes (miRNAs) encoding small noncoding RNAs that can regulate gene expression. The main mechanism of microRNoma (defined as the full complement of microRNAs present in a genome) alteration in cancer cell seems to result in aberrant gene expression characterized by abnormal levels of expression for mature and/or precursor miRNA sequences in comparison with the corresponding normal tissues. Loss or amplification of miRNA genes has been reported in a variety of cancers, and altered patterns of miRNA expression may affect cell cycle and survival programs. The causes of the widespread differential expression of miRNA genes between malignant and normal cells can be explained by the genomic location of these genes in cancer-associated genomic regions, by epigenetic mechanisms as well as by alterations of members of the processing machinery. Germline and somatic mutations in miRNAs or polymorphisms in the mRNAs targeted by miRNAs may also contribute to cancer predisposition and progression. miRNAs expression profiling has been exploited to identify miRNAs potentially involved in the pathogenesis of human cancers and has allowed the identification of signatures associated with diagnosis, staging, progression, prognosis, and response to treatment of human tumors. Here we present a flowchart of principal steps to produce, analyze, and understand the biological significance of miRNA microarray data.