Thyroid cancer is one of the most common endocrine pathologies. Among the various histotypes of thyroid cancer there are both the more indolent and the more aggressive types. Thyroid cancer initiation and progression occurs through gradual accumulation of various genetic and epigenetic alterations that activates pathways, that causes the silencing of thyroid-specific genes and shuts off the iodide-handling machinery.
The decrease of the iodine uptake is correlated to the de-differentiation of thyroid cancer cells.
The recent advances in cell biology allowed by the development of 3D culture method led us to establish five lines of patient-derived thyroid cancer organoids. The 3D culture method permits cells to grow similar in vivo, to maintain the structure of the tissue they originate and the cell polarization, thanks to specific nutrients and supplements that maintain the self-renew features of de-differentiated cells.
Recent literature data about miR-139-5p shown a gradual reduction of its abundance from healthy thyroid to adenoma, differentiated thyroid cancer, and poorly differentiated thyroid cancer.
Data collected by a network approach adopted in our laboratory to analyze The Cancer Genome Atlas Project expression data, revealed that among mir-335-5p targets there are the upregulated genes in thyroid cancer and the majority were involved in iodine metabolism. Moreover mir-335-5p is downregulated in the thyroid cancer commercial cell lines.
Given this data, the aim of the project is verifying the involvement of the two miRNAs in the regulation of iodine uptake in thyroid cancer, and the role of mir-139-5p and mir-335-5p in thyroid cancer phenotype using as model the five organoids thyroid cancer cell lines.
This project aims is to try to understand the molecular mechanisms underlying the carcinogenesis process in the context of thyroid carcinoma, studying its metabolism in different conditions. In particular, we will use basic molecular biology techniques such as real-time for expression analysis and immunofluorescence for protein intracellular localization but applied to the latest 3-dimensional culture methods. Moreover, until now, there are no data for patient-derived thyroid cancer organoids.