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Published on: August 23, 2019
The role of miR-139-5p in radioiodine-resistant thyroid cancer
V Pecce1, M Sponziello1, A Verrienti2
1Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
Purpose:
Radioiodine I-131 (RAI) is the therapy of choice for differentiated thyroid cancer (DTC). Between 5% and 15% of DTC patients become RAI refractory, due to the loss of expression/function of iodide metabolism components, especially the Na/I symporter (NIS). We searched for a miRNA profile associated with RAI-refractory DTC to identify novel biomarkers that could be potential targets for redifferentiation therapy.
Methods:
We analyzed the expression of 754 miRNAs in 26 DTC tissues: 12 responsive (R) and 14 non-responsive (NR) to RAI therapy. We identified 15 dysregulated miRNAs: 14 were upregulated, while only one (miR-139-5p) was downregulated in NR vs. R tumors. We investigated the role of miR-139-5p in iodine uptake metabolism. We overexpressed miR-139-5p in two primary and five immortalized thyroid cancer cell lines, and we analyzed the transcript and protein levels of NIS and its activation through iodine uptake assay and subcellular protein localization.
Results:
The finding of higher intracellular iodine levels and increased cell membrane protein localization in miR-139-5p overexpressing cells supports the role of this miRNA in the regulation of NIS function.
Conclusions:
Our study provides evidence of miR-139-5p involvement in iodine uptake metabolism and suggests its possible role as a therapeutic target in restoring iodine uptake in RAI-refractory DTC.
Insights
MicroRNA-139-5p may restore radioiodine therapy effectiveness in refractory differentiated thyroid cancer. This study found miR-139-5p enhances iodine uptake, suggesting it as a therapeutic target for redifferentiation therapy.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Differentiated thyroid cancer (DTC) is typically treated with radioiodine I-131 (RAI).
- 5-15% of DTC patients develop RAI resistance, often due to impaired iodide metabolism via the sodium-iodide symporter (NIS).
- Identifying biomarkers for RAI resistance is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To identify microRNA (miRNA) profiles associated with RAI-refractory DTC.
- To investigate the role of specific miRNAs in regulating iodide metabolism.
- To explore potential therapeutic targets for redifferentiation therapy in RAI-refractory DTC.
Main Methods:
- Analyzed miRNA expression in 26 DTC tissues (12 RAI-responsive, 14 RAI-non-responsive).
- Identified 15 dysregulated miRNAs, including one downregulated miRNA, miR-139-5p.
- Overexpressed miR-139-5p in thyroid cancer cell lines to assess its impact on NIS function and iodine uptake.
Main Results:
- miR-139-5p overexpression led to increased intracellular iodine levels.
- Enhanced miR-139-5p promoted NIS protein localization to the cell membrane.
- These findings support miR-139-5p's role in regulating NIS function and iodine uptake.
Conclusions:
- miR-139-5p is involved in regulating iodine uptake metabolism.
- miR-139-5p represents a potential therapeutic target for restoring iodine uptake in RAI-refractory DTC.
- Further research into miR-139-5p could lead to effective redifferentiation therapies.
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