microRNAs (miRNA or μRNA) are single-stranded RNA molecules of 21-23 nucleotides in length, which regulate gene expression. miRNAs are encoded by genes from whose DNA they are transcribed but miRNAs are not translated into protein (i.e. they are non-coding RNAs); instead each primary transcript (a pri-miRNA) is processed into a short stem-loop structure called a pre-miRNA and finally into a functional miRNA. Mature miRNA molecules are partially complementary to one or more messenger RNA (mRNA) molecules, and their main function is to down-regulate gene expression.
A variety of studies have shown the ability of individual miRNAs to regulate oncogene and tumor suppressor gene expression and others have shown that miRNA gene loss or mutation can contribute to tumorigenesis. miRNA expression patterns (or signatures) are now known to characterize the developmental origins of tumors more effectively than mRNA expression signatures and may provide a useful tool for the diagnosis and prognosis of human cancer. Several approaches have been developed to block the function of miRNAs resulting in the inhibition of their oncogenic effects. These accomplishments have revealed a potential for miRNA to be used as a clinical tool in cancer diagnosis and as a target for therapy.
Researchers found that the levels of the primary or mature microRNAs derived from the mir-17–92 locus are often substantially increased in the cancers. The studies indicate that non-coding RNAs, specifically microRNAs, can modulate tumour formation, and implicate the mir-17–92 cluster as a potential human oncogene. Recent evidence has shown that miRNA misexpression correlates with progression of various human cancers. There were findings highlight the potential of the Fli-3 encoding mir-17–92 in the development of erythroleukemia and its important role in hematopoiesis.
Another study found that two types of miRNA inhibit the E2F1 protein, which regulates cell proliferation. miRNA appears to bind to messenger RNA before it can be translated to proteins that switch genes on and off. By measuring activity among 217 genes encoding miRNA, patterns of gene activity that can distinguish types of cancers can be discerned. miRNA signatures may enable classification of cancer. This will allow doctors to determine the original tissue type which spawned a cancer and to be able to target a treatment course based on the original tissue type. miRNA profiling has already been able to determine whether patients with chronic lymphocytic leukemia had slow growing or aggressive forms of the cancer. In 2008, the companies Asuragen and Exiqon were working to commercialize this potential for miRNAs to act as cancer biomarkers.
The presence of miRNAs in clinical samples such as saliva, as well as disease state and patient prognosis, suggests that miRNAs may ultimately prove to be valuable cancer diagnostic analytes.
Researchers continue to add to the diagnostic alphabet of saliva by identifying the presence of at least 50 microRNAs that could aid in the detection of oral cancer, according to a report in Clinical Cancer Research, a journal of the American Association for Cancer Research. David T. Wong, D.M.D., D.M.Sc., Felix and Mildred Yip Endowed Professor at the University of California, Los Angeles School of Dentistry and colleagues measured microRNA levels in the saliva of 50 patients with oral squamous cell carcinoma and 50 healthy control patients. They detected approximately 50 microRNAs. Two specific microRNAs, miR-125a and miR-200a, were present at significantly lower levels in patients with oral cancer than in the healthier controls. This latest research offers another minimally invasive, cost-effective method for early detection of the disease that can be translated to earlier treatment and potential improvement in long-term survival rates.
Lee RC, Feinbaum RL, Ambros V (December 1993). ”The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14”. Cell 75 (5): 843–54.
Ruvkun G (October 2001). ”Molecular biology. Glimpses of a tiny RNA world”. Science (journal) 294 (5543): 797–9.
Vicki Glaser (2008-03-01). ”Tapping miRNA-Regulated Pathways”. Genetic Engineering & Biotechnology News (Mary Ann Liebert, Inc.).
He L, Thomson JM, Hemann MT, et al. (June 2005). ”A microRNA polycistron as a potential human oncogene”. Nature 435 (7043): 828–33.
Cui JW, Li YJ, Sarkar A, Brown J, Tan YH, Premyslova M, Michaud C, Iscove N, Wang GJ, Ben-David Y. (June 2007). ”Retroviral insertional activation of the Fli-3 locus in erythroleukemias encoding a cluster of microRNAs that convert Epo-induced differentiation to proliferation.”. Blood 110: 2631-40.
O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT (June 2005). ”c-Myc-regulated microRNAs modulate E2F1 expression”. Nature 435 (7043): 839–43.
Lu J, Getz G, Miska EA, et al. (June 2005). ”MicroRNA expression profiles classify human cancers”. Nature 435 (7043): 834–8.
BioSpace (2007-11-27). ”Exiqon A/S To Acquire Oncotech”. Press release. Retrieved 2008-05-16. “The transaction will create a world leader in molecular diagnostic products based on miRNA.”
Noh Jin Park, Hui Zhou, David Elashoff, Bradley S. Henson, Dragana A. Kastratovic, Elliot Abemayor, and David T. Wong. ”Salivary microRNA: Discovery, Characterization, and Clinical Utility for Oral Cancer Detection”. Clin Cancer Res 2009;15(17).