A truth serum for cancer—microRNAs have major potential as cancer biomarkers

LJ Chin, FJ Slack - Cell research, 2008 - nature.com
LJ Chin, FJ Slack
Cell research, 2008nature.com
Identification of biological markers of cancer is a major area of research. Biomarkers could
identify the presence of a tumor before it could otherwise be easily detected, and the ability
to detect cancers at early stages is a key factor in increasing survivability. For example, the
American Cancer Society finds that a reason breast cancer survival rates are so high is that
there are good methods for early detection of tumors. However, this is not the case for most
cancers. For lung cancer, the five-year survival is 15%, but for the 16% of lung cancer cases …
Identification of biological markers of cancer is a major area of research. Biomarkers could identify the presence of a tumor before it could otherwise be easily detected, and the ability to detect cancers at early stages is a key factor in increasing survivability. For example, the American Cancer Society finds that a reason breast cancer survival rates are so high is that there are good methods for early detection of tumors. However, this is not the case for most cancers. For lung cancer, the five-year survival is 15%, but for the 16% of lung cancer cases diagnosed at early stages, the five-year survival rate is 49%[1]. While this is just one example, the ability to identify a cancer while it is still localized is clearly beneficial. Currently, most methods for discovering and testing tumor biomarkers are difficult and labor-intensive procedures, and at most, only several markers can be tested for at one time. However, due to the simplicity of getting a blood sample, easily testable biomarkers found in blood serum would be especially useful. Just recently, scientists have begun identifying microRNAs (miRNAs) as cancer biomarkers [2-4]. MiRNA genes code for a relatively new class of regulatory RNAs that are~ 22 nucleotides long. miRBase (Release 12.0), the central database for miRNAs, lists over 8 000 miRNAs from plants, animals and viruses. Many miRNAs are well conserved across species, suggesting an important role for them. MiRNA biogenesis and regulation of gene expression have been extensively covered in numerous reviews [5-7]. Briefly, most mature miRNAs are the products of RNA polymerase II-transcribed transcripts that have been processed by two RNase III enzymes, Drosha and Dicer. The mature miRNA is incorporated into an RNA-induced silencing complex that binds to a target messenger RNA (mRNA). In animals, miRNAs bind with imperfect complementarity to the 3′ untranslated region of their targets to inhibit gene expression through several possible mechanisms, including degradation of the mRNA, inhibition of the initiation or elongation steps of translation, and localization to cytoplasmic P-bodies. Because animal miRNAs bind with imperfect complementarity, miRNAs are though to be capable of targeting numerous mRNAs; thus, misexpression of one miRNA can disrupt the expression of hundreds of proteins.
Although first discovered in C. elegans, miRNAs have since been shown to be involved in human cancers [5]. A number of miRNA genes were shown to be located in fragile regions of the human genome that are associated with cancer [8]. Furthermore, miRNAs are continuously being shown to act as both oncogenes and tumor suppressors [5]. With the development of technologies to look at the expression levels of
nature.com