In conclusion, miR-146b-5p expression correlated with advanced PTC and promoted PTC development by targeting CCDC6 in vitro and in vivo; it could, therefore, serve as a promising target for PTC treatment.
Our results suggested the important roles of ITGA2, FN1, ICAM1, TIMP1 and CDH2 in the progression of PTC. miR-204-5p, miR-7-2, and miR-146b are potential biomarkers for PTC staging and FN1, CLDN1, and TNFRSF12A may serve as markers of prognosis in PTC.
The results indicated that the expression levels of serum miR-222, miR-221 and miR-146b were significantly increased in patients with newly diagnosed PTC compared with controls and patients with BTN.
Based on our findings, the expression of miR-146a and miR-146b correlates with the occurrence and prognosis of papillary thyroid carcinoma, and the expression levels of miR-146a and miR-146b seem to affect the cell proliferation and migration and regulate the expression of IRAK1 protein in cancer cells.
In conjunction with the current perspectives on miRNAs in a wide variety of human cancers, this review will hopefully translate these updated findings on miR-146b into more comprehensive diagnostic or prognostic information regarding treatment in PTC patients before surgical intervention and follow up strategies.
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.
Relative expression of six microRNAs (miR-146b, -21, -221, -222, 375, -199b) appeared significantly different in BRAF(V600E)-positive samples (all classified as papillary thyroid carcinomas) compared to BRAF(V600E)-negative papillary carcinoma samples.
For discrimination between benign and PTC lesions, the area under the ROC curve (AUC) for miR-146b was 0.649 with 61.4% sensitivity and 57.9% specificity.
Recent microRNA analysis revealed an association between miR146b and the BRAF mutation, which was associated with poor prognosis of papillary thyroid carcinoma (PTC).
In order to examine the expression of miR-146b-5p and miR-21 in benign and malignant thyroid tissues and to determine if these microRNAs could be assigned to distinct histomorphological types of thyroid nodules, we analyzed miR-146b-5p and miR-21 expression in thyroid nodules on tissue microarrays (TMAs) with 193 thyroid specimens by ISH. miR-146b-5p and miR-21 expression in thyroid tissues was also analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). miR-146b-5p was highly expressed (89%) in papillary thyroid carcinomas (PTCs) and 41% of FVPTC.
The results showed that PTC cells overexpress miR-146b and miR-222 in exosomes; and that factors released by both normal thyroid and PTC cells alter proliferation of other cells in a complex manner.
These results indicate that miR-146b-5p induces EMT and may promote PTC metastasis through the regulation of Wnt/β-catenin signaling, and suggest novel potential therapeutic targets for the treatment of PTC.
Furthermore, our findings show that miR-146b and PAX8 regulate each other and share common target genes, thus highlighting a novel regulatory circuit that governs the differentiated phenotype of PTC.
Eleven miRNAs were significantly differentially expressed between nodular goiter and PTC and between highly invasive and low invasive PTC. miR-199b-5p and miR-30a-3p were significantly differentially expressed among the three groups. miR-30a-3p, miR-122-5p, miR-136-5p, miR-146b-5p and miR-199b-5p were selected for further study by qRT-PCR and miR-146b-5p, miR-199b-5p and miR-30a-3p were different between the PTC and nodular goiter groups. miR-199b-5p was over-expressed in PTC patients with extrathyroidal invasion and cervical lymph node metastasis.
MicroRNA-222 and miR-146b were over-expressed 10.8-fold and 8.9-fold, respectively, in Rc-PTC tumors compared with NR-PTC tumors (P = .014 and P = .038, respectively).
Significant miRNA deregulation was confirmed in the validation cohort, with upregulation of miR-146b-5p and miR-221/222 and downregulation of miR-16 and miR-613 in aggressive PTCs.
Our results confirm the oncogenic role of miR-146b-5p in thyroid follicular cells and contribute to knowledge regarding the modulation of TGF-β signal transduction by miRNAs in PTCs.
The analysis of miR-146b-5p and let-7f expression revealed a distinct pattern from a cohort of PTC patients, suggesting caution in evaluating miRNA expression data as molecular markers of PTC diagnosis and prognosis.