The role of microRNAs in the pathogenesis and treatment of hematopoietic malignancies.
2012
microRNAs (miRNAs) comprise a recently discovered class of non-coding RNAs with regulatory functions in posttranscriptional
gene expression control. Many miRNAs are located in genomic regions that are frequently deleted in cancer, or are subject
to epigenetic and transcriptional deregulation in cancer cells. The miRNA transcriptome of cancer cells is very different from that of their
normal cell counterparts. miRNAs can exhibit oncogenic or tumor suppressive or even both properties depending on the specific targets
and cellular context. It is becoming increasingly clear that miRNAs not only serve as useful tumor biomarkers with implications for diagnosis,
prognosis and the prediction of treatment responses, but may also be used for targeted cancer treatment and even as therapeutics. In
this review, we provide an overview of recent advances in our understanding of the tumor suppressor miRNAs and oncomiRs involved in
the pathogenesis of leukemias and lymphomas, and their target transcripts in cancer signaling networks. In particular, we focus on the
role of miRNAs in chronic lymphocytic and acute lymphoblastic leukemia and in B-cell lymphomas. In the second part, we review the
various alternative strategies of targeting miRNAs in cancer therapy. Methods of oncomiR antagonization by antagomiRs or locked nucleid
acids are contrasted with strategies that harness the tumor suppressive properties of certain miRNAs for cancer treatment. Preclinical
progress, also with regard to delivery strategies, possible side effects and other pharmacological aspects, is presented along with results
from the first human trials assessing the safety and efficacy of miRNA-targeting therapeutics.
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