Reduced expression of THRβ in papillary thyroid carcinomas: relationship with BRAF mutation, aggressiveness and miR expression

Rosignolo, Francesca; Maggisano, Valentina; Sponziello, Marialuisa; Celano, Marilena; Gioia, Cira Di; D’Agostino, Massimo; Giacomelli, Luciano; Verrienti, Antonella; Dima, Mariavittoria; Pecce, Valeria; Durante, Cosimo

doi:10.1007/s40618-015-0309-4

Cited by 25 publications

(15 citation statements)

References 34 publications

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“…The screening analysis consisted of miRNA profiling performed on fresh-frozen thyroid tissues from cohort I PTC patients. TaqMan Array Human MicroRNA A+b Cards v3.0 (Thermo Fisher Scientific), a set of two 384-well microfluidic cards, were used to quantify the relative expression of 754 miRNAs as previously reported (20). In the validation analysis, we evaluated the expression of a selected panel of miRNAs in FFPE samples of thyroid tissue from cohort II PTC patients using Custom TaqMan Array MicroRNA Cards (Thermo Fisher Scientific).…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-based molecular classification of papillary thyroid carcinoma

Rosignolo

Memeo²,

Monzani

et al. 2017

International Journal of Oncology

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MicroRNA (miRNA) expression is dysregulated in many human malignancies, and a growing number of studies are focused on their potential use as tumor biomarkers. To identify a miRNA signature for papillary thyroid carcinomas (PTC), we investigated miRNA expression profiles in two independent cohorts of PTCs, which included major histological subtypes [classical-type (PTC‑CT), follicular-variant (PTC‑FV), and tall-cell variant (PTC‑TCV)] and cases with low or intermediate risk of recurrence. Using TaqMan® Array Human MicroRNA A+B Cards v3.0, we first performed microRNA profiling of normal and neoplastic thyroid tissues from 29 PTC patients. Promising candidates were then investigated in a second, independent cohort of 76 PTCs using Custom TaqMan® Array MicroRNA Cards. We identified a molecular signature of 11 miRNAs that were significantly upregulated (miR‑146b-5p, miR‑146b-3p, miR‑221-3p, miR‑222‑5p, miR‑222‑3p) or downregulated (miR‑1179, miR‑486‑5p, miR‑204-5p, miR‑7-2-3p, miR‑144-5p, miR‑140-3p) in PTC tissues vs. normal thyroid tissue. Upregulation of miR‑146b-5p and miR‑222‑3p was also significantly associated with an increased risk of recurrence. Higher than normal expression of miR‑146b-5p and miR‑146b-3p characterized PTC‑CT and PTC‑TCV but not PTC‑FV, whereas miR‑21-5p was significantly upregulated only in PTC‑TCV. When PTC‑FV were subclassified as encapsulated (PTC‑EFV) or infiltrative (PTC‑IFV), miR‑204-5p was downregulated in all histological subtypes except PTC‑EFV, which displayed expression levels similar to those of normal thyroid tissues. These findings provide new insights into the molecular classification of PTC, showing that different miRNA expression profiles are associated with different histological types of PTC and different risks of recurrence.

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Section: Methodsmentioning

confidence: 99%

MicroRNA-based molecular classification of papillary thyroid carcinoma

Rosignolo

Memeo²,

Monzani

et al. 2017

International Journal of Oncology

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“…PAX8 mRNA levels were assessed in surgical specimens of 36 PTCs collected between 2008 and 2014 at the University of Rome. All have been analyzed in previous reports [ 13 , 14 ]. Thirty-one of the tumors were classical-type (CT-PTCs) and the remaining five were follicular-variants (FV-PTCs).…”

Section: Methodsmentioning

confidence: 99%

Expression of PAX8 Target Genes in Papillary Thyroid Carcinoma

et al. 2016

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PAX8 is a thyroid-specific transcription factor whose expression is dysregulated in thyroid cancer. A recent study using a conditional knock-out mouse model identified 58 putative PAX8 target genes. In the present study, we evaluated the expression of 11 of these genes in normal and tumoral thyroid tissues from patients with papillary thyroid cancer (PTC). ATP1B1, GPC3, KCNIP3, and PRLR transcript levels in tumor tissues were significantly lower in PTCs than in NT, whereas LCN2, LGALS1 and SCD1 expression was upregulated in PTC compared with NT. Principal component analysis of the expression of the most markedly dysregulated PAX8 target genes was able to discriminate between PTC and NT. Immunohistochemistry was used to assess levels of proteins encoded by the two most dyregulated PAX8 target genes, LCN2 and GPC3. Interestingly, GPC3 was detectable in all of the NT samples but none of the PTC samples. Collectively, these findings point to significant PTC-associated dysregulation of several PAX8 target genes, supporting the notion that PAX8-regulated molecular cascades play important roles during thyroid tumorigenesis.

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“…Tissue samples were excluded if tumor sample cellularity was less than 60%, and/or if normal thyroid tissue from the uninvolved lobe exhibited signs of inflammation or other types of disease. All 86 PTCs were also used to study the expression of thyroid-specific differentiation markers, and those results have been described elsewhere (Sponziello et al, 2015;Rosignolo et al, 2015).…”

Section: Collection Of Thyroid Tissuesmentioning

confidence: 99%

Fibronectin-1 expression is increased in aggressive thyroid cancer and favors the migration and invasion of cancer cells

Sponziello

Rosignolo

Celano

et al. 2016

Molecular and Cellular Endocrinology

119

100

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In this study we analyzed the expression levels of markers of epithelial-to-mesenchymal transition (EMT) in several papillary thyroid carcinomas (PTCs) and the relation with tumor genotypes and clinicopathological characteristics. The role of fibronectin-1 (FN1) was investigated by analyzing the effects of FN1 silencing in two human thyroid cancer cell lines. Most of EMT markers were significantly over-expressed in a group of 36 PTCs. In particular, FN1 mRNA levels were higher in tumor vs non-tumor tissue (117.3, p < 0.001) and also in aggressive and BRAF(V600E) samples. Similar results were observed (and confirmed at the protein level) when FN1 expression was analyzed in a validation group of 50 PTCs and six lymph node (LN) metastases. Silencing of FN1 in TPC-1 and BCPAP thyroid cancer cells significantly reduced proliferation, adhesion, migration, and invasion in both cell lines. Collectively, our data indicate that FN1 overexpression is an important determinant of thyroid cancer aggressiveness.

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Reduced expression of THRβ in papillary thyroid carcinomas: relationship with BRAF mutation, aggressiveness and miR expression

Cited by 25 publications

References 34 publications

MicroRNA-based molecular classification of papillary thyroid carcinoma

MicroRNA-based molecular classification of papillary thyroid carcinoma

Expression of PAX8 Target Genes in Papillary Thyroid Carcinoma

Fibronectin-1 expression is increased in aggressive thyroid cancer and favors the migration and invasion of cancer cells

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