ECE2021 Oral Communications Oral Communications 5: Thyroid (6 abstracts)
Role of miR-139–5p in radioiodine-refractory thyroid cancers
Valeria Pecce 1 , Luana Abballe 2 , Marialuisa Sponziello 1 , Chiara Brunelli 3 , Antonella Verrienti 1 , Salvatore Annunziata 4 , Giorgio Grani 1 , Guido Fadda 5 , Massimo Salvatori 4 , Diego Russo 6 & Cosimo Durante 1
1Sapienza University of Rome, Department of Translational and Precision Medicine, Rome, Italy; 2IRCCS Ospedale Pediatrico Bambino Gesù, Department of Pediatric Hematology/Oncology and Cell and Gene Therapy, Rome, Italy; 3IRCCS Policlinico Agostino Gemelli, Unit of Anatomic Pathology, Rome, Italy; 4IRCCS Policlinico Agostino Gemelli, Rome, Italy; 5A.O.U. Policlinico G. Martino, Section of Pathological Anatomy, Department of Human Pathology “Gaetano Barresi”, Messina, Italy; 6Università di Catanzaro “Magna Graecia”, Department of Health Sciences, Catanzaro, Italy
Radioiodide 131I (RAI) is the therapy of choice for radioiodine-avid differentiated thyroid cancer (DTC). However, 5–15% of DTC patients become RAI refractory (RAIR), and the 10-year survival rate for metastatic disease decreases to 10%. The failure of RAI response is mainly due to the loss of thyroid differentiation, that leads to the loss of expression/function of components of iodide metabolism, first of all the Na/I symporter (NIS). The finding that the MAPK pathway is involved in this process suggested that the protein kinase inhibitors therapy may be effective for redifferentiation in the treatment of RAIR patients. However, nowadays, fully efficient treatments for advanced thyroid cancer patients are still missed. Different approaches aimed to re-activate radioiodine uptake in RAIR tumors have been trying, including the use of a miRNA-based strategy. Although MiRNAs have been shown to be useful predictive biomarkers and targets of therapeutic options in thyroid cancers, only few studies investigated their role in response to RAI therapy. We investigated the miRNA signature associated with RAI refractory DTC in order to identify novel biomarkers that will be potential target for a redifferentiation therapy. Using the real-time PCR we analysed the expression of 734 miRNA in 26 DTC tissues, 13 responsive (R) and 13 not-responsive (NR) to RAI therapy. By comparing both groups we found a statistically significant dysregulation of 15 miRNAs analysed: 14 miRNAs were upregulated and only one (miR-139–5p), was down-regulated in RAI refractory tumors. Then, we performed in-vitro experiments to investigate the role of miR-139–5p in the iodine uptake metabolism. Using two primary cell lines and five immortalized cell lines, we overexpressed miR-139–5p, and we analysed the transcript and protein levels of NIS. Moreover, we investigate the NIS activation status through the iodine uptake assay and the subcellular protein localization. The findings of a higher intracellular iodine level and of an increase in cells’ membrane protein localization in miR-139–5p overexpressing cells, supported the effect of such miRNA in increasing NIS function. Although the downregulation of miR-139–5p expression has already been found to correlate with the thyroid cancer’s aggressiveness, this is the first study aimed to investigate its role in the iodine uptake metabolism. However further studies are necessary to confirm the possible role of miR-139–5p as therapeutic target for RAI refractory DTCs.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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