Family of microRNA-146 Regulates RARβ in Papillary Thyroid Carcinoma
Open Access
- 24 March 2016
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 11 (3), e0151968
- https://doi.org/10.1371/journal.pone.0151968
Abstract
Retinoic acid is a promising tool in adjuvant cancer therapies, including refractory thyroid cancer, and its biological role is mediated by the retinoic acid receptor beta (RARβ). However, expression of RARβ is lowered in papillary thyroid carcinoma (PTC), contributing to promotion of tumor growth and inefficiency of retinoic acid and radioactive iodine treatment. The causes of aberrant RARB expression are largely unknown. We hypothesized that the culpable mechanisms include the action of microRNAs from the miR-146 family, previously identified as significantly upregulated in PTC tumors. To test this hypothesis, we assessed the expression of RARB as well as miR-146a-5p and miR-146b-5p in 48 PTC tumor/normal tissue pairs by Taqman assay to reveal that the expression of RARB was 3.28-fold decreased, and miR-146b-5p was 28.9-fold increased in PTC tumors. Direct interaction between miRs and RARB was determined in the luciferase assay and further confirmed in cell lines, where overexpression of miR-146a-5p and miR-146b-5p caused a 31% and 33% decrease in endogenous RARB mRNA levels. Inhibition of miR-146a and miR-146b resulted in 62.5% and 45.4% increase of RARB, respectively, and a concomitant decrease in proliferation rates of thyroid cancer cell lines, analyzed in xCELLigence system.We showed that two microRNAs of the miR-146 family directly regulate RARB. Inhibition of miRs resulted in restoration of RARB expression and decreased rates of proliferation of thyroid cancer cells. By restoring RARB levels, microRNA inhibitors may become part of an adjuvant therapy in thyroid cancer patients.Keywords
This publication has 39 references indexed in Scilit:
- Thyroid Hormone Receptor β (THRB) Is a Major Target Gene for MicroRNAs Deregulated in Papillary Thyroid Carcinoma (PTC)Journal of Clinical Endocrinology & Metabolism, 2011
- Retinoic acid therapy in patients with radioiodine negative differentiated thyroid cancer and clinical or biochemical evidence of disease: An initial experienceIndian Journal of Nuclear Medicine, 2011
- Stromal retinoic acid receptor β promotes mammary gland tumorigenesisProceedings of the National Academy of Sciences, 2010
- DNA methylation changes in normal liver tissues and hepatocellular carcinoma with different viral infectionExperimental and Molecular Pathology, 2010
- 13-cis-retinoic acid re-differentiation therapy and recombinant human thyrotropin-aided radioiodine treatment of non-Functional metastatic thyroid cancer: a single-center, 53-patient phase 2 studyThyroid Research, 2009
- Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancerProceedings of the National Academy of Sciences, 2009
- Recent Advances in Molecular Biology of Thyroid Cancer and Their Clinical ImplicationsOtolaryngologic Clinics of North America, 2008
- Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinomaProceedings of the National Academy of Sciences, 2008
- Effect of all-trans retinoic acid on sodium/iodide symporter expression, radioiodine uptake and gene expression profiles in a human anaplastic thyroid carcinoma cell lineNuclear Medicine and Biology, 2006
- Direct growth stimulation of normal human epithelial cells by mutant p53Molecular Carcinogenesis, 1993