Krystian Jazdzewski, MD, PhD, Affiliate
College of Medicine
Molecular Virology, Immunology & Medical Genetics
Res Asst Professor
Molecular Biology and Cancer Genetics
Thyroid Neoplasms, Carcinoma, Papillary, Graves Disease, Graves Ophthalmopathy, Autoimmunity, Carcinoma, Neoplasms, Eye Diseases, Cardiovascular Diseases
The evolving awareness of microRNAs (miRs) and other non-coding RNA genes was beginning to hint that miRs might be responsible for some of the strong genetic predisposition displayed by thyroid cancer. Dr. Jazdzewski performed genetic association studies that clearly suggested such a role for miR-146a. The study, designed to determine the mechanism involved, produced exciting results, as it showed that the rare allele in the polymorphism of pre-miR-146a has almost totally lost the ability to produce mature miR. Moreover, 4.7% of tumors had undergone somatic mutations of the SNP sequence. Thus, Dr. Jazdzewski’s data showed that a common polymorphism in microRNA gene affects the miR expression, contributes to the genetic predisposition to thyroid cancer, and plays a role in the tumorigenesis through somatic mutation (PNAS, 2008). The miR-146a proved to be the first gene predisposing to papillary thyroid carcinoma focusing attention of the field on the role of non-coding RNA genes in thyroid tumorigenesis. Dr. Jazdzewski continued his research on microRNA genes and made another discovery: that an “innocent” genomic alteration such as a SNP when located in the pre-miR sequence can lead to the production of 2 miRs, each with its distinct set of target genes (PNAS, 2009). The realization that this can occur carries potentially far-reaching consequences for our understanding of what miRs do and underscores the role of variations within miR sequence. In his recent work Dr. Jazdzewski addressed the functional consequences of the upregulation of microRNA genes found in thyroid cancer. Dr. Jazdzewski’s group queried what genes were regulated by those miRs that were overexpressed in thyroid tumors and, surprisingly, noticed that the top seven miRs deregulated in thyroid tumors were predicted to bind to the same single gene, namely THRB, a known tumor-supressor gene. In further experiments they proved that an up-regulation of microRNAs might well be an important mechanism of silencing of THRB, and inhibition of function of thyroid hormones in human cancers (JCEM, 2011).