The expression and function of miRNAs in thyroid neoplasia

Abstract

Thyroid cancer is the most common endocrine malignancy and accounts for the majority of endocrine cancer deaths each year. Carcinomas of the thyroid comprise a heterogeneous group of neoplasms with distinctive clinical and pathological characteristics. The majority of thyroid tumours are designated as papillary thyroid cancer (PTC) and are well differentiated, indolent and are associated with good prospects of survival. Undifferentiated or anaplastic carcinomas (ATC), however, are very aggressive with survival rates of less than one year in most instances. microRNAs (miRNA) are a family of short non-protein-coding RNAs with diverse functions, including regulation of cellular differentiation, proliferation and apoptosis. These RNAs negatively regulate gene expression by targeting mRNAs for degradation or translational repression. Studies have indicated that different populations of miRNAs are expressed in cancer and normal tissues, in fact altered miRNA expression has been detected in every cancer in which miRNA expression signatures have been examined. These signatures are often proposed as biomarkers of cancer. miRNAs are capable of acting as both tumour suppressors and oncogenes; and they can also target oncogenes and tumour suppressor genes to promote cancer progression. Studies on miRNA expression in PTC have found an aberrant miRNA expression profile in PTCs compared with normal thyroid tissues and have identified certain miRNAs that have become associated with this disease, such as miR-221, miR-222, and miR-146. The objective of this thesis was to further characterise the expression and role of miRNAs in thyroid carcinoma.