Serum microRNAs as non-invasive biomarkers for cancer

In this review, we discuss recent findings indicating that circulating microRNAs are useful as non-invasive biomarkers for different tumor types. Additionally, we summarize the knowledge about the mechanism of microRNA release and the putative functional roles of circulating microRNAs. Although several challenges remain to be addressed, circulating microRNAs have the potential to be useful for the diagnosis and prognosis of cancer diseases.One of the major challenges in cancer research is the identification of stable biomarkers, which can be routinely measured in easily accessible samples. Over many decades it has been shown that cell-free DNA and RNA is present in serum and other body fluids and that these circulating nucleic acids may represent potential biomarkers (reviewed in [1-3]). One decade ago, microRNAs (miRNAs) were discovered as a novel class of evolutionarily conserved small (18 - 24 nucleotides) non-coding RNA molecules, which are important regulators of gene expression [4,5]. By targeting the 3' untranslated region (UTR) of mRNA transcripts, miRNAs influence RNA stability and translational efficiency via degradation or protein translation inhibition, respectively [4,6-9]. Thus, alterations in miRNA-expression can affect crucial biological processes in cancer development and progression, such as proliferation, differentiation and apoptosis [10,11]. For example, the well-described let 7 miRNA family is evolutionary conserved from C. elegans to humans and has been shown to directly target the human RAS oncogenes [12]. In humans, significantly reduced expression of let-7 family members has been found in various cancers including lung, colon, ovarian, and gastric cancer, as well as leiomyoma and melanoma [13]. Its decreased expression is associated with a significantly shorter survival of lung cancer patients and promotes the colony forming ability of lung cancer cells in vitro [14]. miRNA 221 and miRNA 222 are located on chromosome X, and have been report