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Title: The miR-146b-3p/PAX8/NIS Regulatory Circuit Modulates the Differentiation Phenotype and Function of Thyroid Cells During Carcinogenesis      
dateReleased:
08-24-2015
description:
To comprehensively characterize microRNAs (miRNA) expression and their target genes in thyroid cancer, we performed next-generation sequencing expression analysis of this disease. Recent studies have found that only the most abundant microRNAs mediate significant target suppression. We sequenced small RNA from 8 papillary thyroid carcinomas (PTC) with paired samples of normal thyroid tissue. We found that only a small set of abundant miRNAs are differentially expressed after pair-wise comparison (12 upregulated and 8 downregulated) reaching the minimum threshold amount to repress target mRNAs. We integrated computational prediction of potential targets and mRNA sequencing from the paired normal and tumor thyroid tissues from the same eight patients with PTC. The integrated analyses identified a master microRNA regulatory network in PTC that is involved in essential biological processes such as thyroid differentiation. As both mature products of miR-146b (miR-146b-5p and -3p) were among the most abundant upregulated in tumors, we unveil their target genes and found that miR-146b-3p specifically binds to the 3`UTR of PAX8 and NIS, leading to an impaired translation of the proteins and subsequently decreasing the iodide uptake of the cells. Furthermore, we show that mir-146b and PAX8 regulate each other, describing a novel regulatory circuit that determines the differentiated phenotype of PTC. In conclusion, our integrative genomic analysis uncovers the target genes of two of the most upregulated miRNAs and highlights the importance of a miR-146b3p-PAX8-NIS regulatory circuit that determines thyroid differentiation in thyroid cancer. Samples from Papillary Thyroid Carcinoma tumors (n=8) and contralateral normal thyroid tissue from the same patient (n=8) were collected at the Biobank of the Hospital Universitario La Paz (Madrid, Spain). The clinical characteristics of patients are summarized in Table S1. Surgically removed tissues were quickly frozen in liquid nitrogen until analysis. The samples were snap frozen on dry ice and stored at -80°C.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-63511
refinement:
raw
alternateIdentifiers:
63511
keywords:
functional genomics
dateModified:
08-29-2015
availability:
available
types:
gene expression
name:
Homo sapiens
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-63511/E-GEOD-63511.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-63511/E-GEOD-63511.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE63511
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
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