Cancers of the head and neck too often fall in between the cracks of medicine and dentistry, resulting in late diagnosis that brings poor prognosis and disfiguring treatments. There is no more important development in early detection and improved survival of oral cancer than an inexpensive non-invasive test that could be part of routine checkups and is simple enough to be performed at health fairs and safety net clinics by a variety of health care professionals and auxiliaries. MicroRNA (miRNA) holds the key to the development of such a test. MiRNAs are a new class of molecule, approximately 20-23 nucleotides in length, which are encoded in the genome and function in the regulation of gene expression at the post-transcriptional level. They act as molecular “rheostats” to make fine-tuning adjustments to protein output. A single change in a miRNA can affect hundreds, or even thousands, of protein expressions. Thus, changes in miRNA profiles appear to play important roles in cell growth and differentiation, as well as in disease states such as cancer. The current project focuses on obtaining profiles of miRNA expression in oral cancer to identify important changes that are relevant to one or more subtypes of oral cancer, as well as elucidating salivary miRNA biomarkers for early oral cancer detection.
This work is supported in part by a Student Fellowship from the Andrew J. Semesco Foundation, Ocala, FL.
Current Project Members
- Amani Harrandah, BDS
- Kristianna Fredenburg, M.D., Ph.D., Dept. of Pathology, Immunology, and Laboratory Medicine, UF College of Medicine, Gainesville, FL
- Jin Q. Cheng, Ph.D., M.D., Dept. of Oncologic Sciences, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Harrandah, A., Fitzpatrick, S.G., Smith, M.H., Wang, D., Cohen, D.M., and Chan, E.K. MicroRNA-375 as a Biomarker for Malignant Transformation in Oral Lesions. Oral Surg Oral Med Oral Pathol Oral Radiol. In press.
Jung, H.M., Benarroch, Y., and Chan, E.K. Anti-cancer drugs reactivate tumor suppressor miR-375 expression in tongue cancer cells. J Cell Biochem. 116:836-43.
Libório-Kimura, T.N., Jung, H.M., and Chan, E.K. miR-494 represses HOXA10 expression and inhibits cell proliferation in oral cancer. Oral Oncol. 51:151-7.
Jung, H.M., Phillips, B.L., and Chan, E.K. miR-375 activates p21 and suppresses telomerase activity by coordinately regulating HPV E6/E7, E6AP, CIP2A, and 14-3-3ζ. Mol Cancer. 13:80.
Jung, H.M., Patel, R.S., Phillips, B.L., Wang, H., Cohen, D.M., Reinhold, W.C., Chang, L.J., Yang, L.J., and Chan, E.K. Tumor suppressor miR-375 regulates MYC expression via repression of CIP2A coding sequence through multiple miRNA-mRNA interaction. Mol Biol Cell. 24:1638-48.
Jung, H.M., Phillips, B.L., Patel, R.S., Cohen, D.M., Jakymiw, A., Kong, W.W., Cheng, J.Q., and Chan, E.K. Keratinization-associated miR-7 and miR-21 regulate tumor suppressor reversion-inducing-cysteine-rich protein with kazal motifs (RECK) in oral cancer. J Biol Chem. 287:29261-72.
Patel, R.S., Jakymiw, A., Yao, B., Pauley, B.A., Carcamo, W.C., Katz, J., Cheng, J.Q., and Chan, E.K. High resolution of microRNA signatures in human whole saliva. Arch. Oral Biol. 56:1506-13.