The Role of microRNAs in the Pathogenesis and Treatment of Hematopoietic Malignancies

Corina      A. Schmid; Vanessa      J. Craig; Anne      Muller; Michael      Flori

doi:10.2174/138161213804805649

Abstract

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.

Keywords: microRNA, post-transcriptional regulation, leukemia and lymphoma, targeted treatment strategies, microRNA replacement therapy, antagomirs, non-coding RNAs, tumor suppressor miRNAs, cancer therapy, transcriptome