Journal Article

Specific microRNAs are downregulated in human thyroid anaplastic carcinomas

Leone, V, Pallante, P, Volinia, S, Borbone, E, Vecchione, A, Calin, G A, Cirombella, R, Troncone, G, Croce, C M, Ferraro, A, Tallini, G, Petrocca, F, Visone, R, Fusco, A, Santoro, M, Coluzzi, S, Ferracin, M, Liu, C-G, Scarpa, A, Colato, C

2007

Overview

Thyroid carcinomas comprise a broad spectrum of tumors with different clinical behaviors. On the one side, there are occult papillary carcinomas (PTC), slow growing and clinically silent, and on the other side, rapidly growing anaplastic carcinomas (ATC), which are among the most lethal human neoplasms. We have analysed the microRNA (miR) profile of ATC in comparison to the normal thyroid using a microarray (miRNACHIP microarray). By this approach, we found an aberrant miR expression profile that clearly differentiates ATC from normal thyroid tissues and from PTC analysed in previous studies. In particular, a significant decrease in miR-30d, miR-125b, miR-26a and miR-30a-5p was detected in ATC in comparison to normal thyroid tissue. These results were further confirmed by northern blots, quantitative reverse transcription–PCR analyses and in situ hybridization. The overexpression of these four miRs in two human ATC-derived cell lines suggests a critical role of miR-125b and miR-26a downregulation in thyroid carcinogenesis, since a cell growth inhibition was achieved. Conversely, no effect on cell growth was observed after the overexpression of miR-30d and miR-30a-5p in the same cells. In conclusion, these data indicate a miR signature associated with ATC and suggest the miR deregulation as an important event in thyroid cell transformation.

• Publisher: Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
• Subject: Apoptosis / Biological and medical sciences / Cancer / Cancer cells / Carcinogenesis / Carcinoma - classification / Carcinoma - genetics / Cell Biology / Cell growth / Cell lines / Cell physiology / Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes / Cell Transformation, Neoplastic / Chromosome Mapping / Chromosomes, Human / DNA microarrays / Endocrinopathies / Fundamental and applied biological sciences. Psychology / Gene expression / Gene Expression Regulation / Genetic aspects / Human Genetics / Humans / Hybridization / Internal Medicine / Malignant tumors / Medical sciences / Medicine / Medicine & Public Health / MicroRNAs / MicroRNAs - genetics / miRNA / Molecular and cellular biology / Neoplasia / Oncology / Physiological aspects / Reference Values / Reverse transcription / RNA / RNA, Neoplasm - genetics / short-communication / Thyroid / Thyroid cancer / Thyroid diseases / Thyroid gland / Thyroid Gland - physiology / Thyroid Neoplasms - classification / Thyroid Neoplasms - genetics / Thyroid. Thyroid axis (diseases) / Tumors