title: Family of microRNA-146 Regulates RARβ in Papillary Thyroid Carcinoma.
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.
authors.affiliation: Genomic Medicine; Medical University of Warsaw, Warsaw, Poland.|Laboratory of Human Cancer Genetics, Centre of New Technologies, CENT, University of Warsaw, Warsaw, Poland.
authors.forename: Agnieszka Anna
authors.initials: AA
authors.lastname: Czajka
authors.affiliation: Genomic Medicine; Medical University of Warsaw, Warsaw, Poland.|Laboratory of Human Cancer Genetics, Centre of New Technologies, CENT, University of Warsaw, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wójcicka
authors.affiliation: Genomic Medicine; Medical University of Warsaw, Warsaw, Poland.|Laboratory of Human Cancer Genetics, Centre of New Technologies, CENT, University of Warsaw, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kubiak
authors.affiliation: Genomic Medicine; Medical University of Warsaw, Warsaw, Poland.|Laboratory of Human Cancer Genetics, Centre of New Technologies, CENT, University of Warsaw, Warsaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Kotlarek
authors.affiliation: Department of Pathology, Maria Skłodowska-Curie Memorial Cancer Center-Institute of Oncology, Warsaw, Poland.
authors.forename: Elwira
authors.initials: E
authors.lastname: Bakuła-Zalewska
authors.affiliation: Department of Pathology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Koperski
authors.affiliation: Department of General and Thoracic Surgery, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Wiesław
authors.initials: W
authors.lastname: Wiechno
authors.affiliation: Genomic Medicine; Medical University of Warsaw, Warsaw, Poland.|Laboratory of Human Cancer Genetics, Centre of New Technologies, CENT, University of Warsaw, Warsaw, Poland.
authors.forename: Krystian
authors.initials: K
authors.lastname: Jażdżewski
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta