Abstract
It is estimated that up to 50% of all human proteincoding genes are regulated by miRNAs. This family of non-coding RNAs, with ∼1500 members reported up-to-date, can impact a variety of cellular processes including cellular proliferation, differentiation and apoptosis. It is not surprising that deregulated expression of selected miRNAs can thus promote cancer initiation and progression. Several miRNAs with oncogenic properties, termed oncomirs, as well as miRNAs with tumor suppressive capabilities have been identified in different malignancies and this list is growing at a rapid pace. MiRNA-based therapies are attractive partly due to the fact that these molecules can target multiple genes in different signaling pathways simultaneously. In addition to their therapeutic potential, miRNAs are released into the circulation and measurement of such species in plasma and serum samples highlights the possibility of leveraging these molecules as potential biomarkers for early cancer detection, prognostic assessment and evaluation of therapeutic response in cancer patients. In this issue of Cancer Biomarkers, Lodewijk et al. discuss differentially expressed miRNAs in subtypes of thyroid cancer: papillary, follicular, anaplastic and medullary thyroid carcinomas. A special interest is placed on the diagnostic potential of miRNAs in this malignancy. The current method utilized to characterize thyroid nodules consisting of fine needle aspiration biopsies is described. Unfortunately, 30% of such biopsies are inconclusive and a hemithyroidectomy is required. Their article thus delves into the potential usefulness of identifying amiRNA signature that would help avoid such a procedure and assist clinicians in discriminating between tumor and benign tissues as well as between tumor types. Similarly, Hogan et al. describe in this issue a need for the identification of novel biomarkers in the early detection of colorectal cancer (CRC). 5-year patient survival is over 90% when detected at an early stage compared with less than 10% survival for stage IV patients. While advantages exist with the currentmethods employed for CRC detection, sensitivity and specificity challenges are discussed and the diagnostic potential of miRNAs is assessed. MiRNA stability and their presence in body fluids including feces make them attractive molecules for the development of noninvasive detection methods for this malignancy. Much effort is also directed towards the identification of a circulating miRNA signature in glioblastoma multiforme (GBM), an aggressive type of brain tumor with dismal prognosis. In this issue, Odjele et al. review the progress made in recent years on identifying miRNAs that would assist clinicians in diagnosing this malignancy. MiRNA levels of miR-128 and miR342-3p vary significantly in blood samples of GBM patients when compared with healthy subjects and are thus emerging as early favorites in the search for a GBM-associated miRNA signature. The article also looks at studies recently undertaken in GBM cell and rodent models that showed promising results on the use
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