Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of micro-RNA genes in human papillary thyroid carcinoma

ABSTRACT: We show that numerous miRNAs are transcriptionally up-regulated in papillary thyroid carcinoma (PTC) tumors compared with unaffected thyroid tissue. Among the predicted target genes of the three most upregulated miRNAs (miRs 221, 222 and 146b), only less than 15% showed significant downexpression in transcript level between tumor and unaffected tissue. The KIT gene which is known to be downregulated by miRNAs 221 and 222 displayed dramatic loss of transcript and protein in those tumors that had abundant mir-221, mir-222, and mir-146b transcript. Experiment Overall Design: Total RNA was extracted from paired tumor and normal thyroid tissues from 9 PTC patients. The same set samples were applied to Custom miRNA microarray chips (OSU_CCC version 2.0) and Affymetrix HG-U133 plus 2 chips.

ORGANISM(S): Homo sapiens

SUBMITTER: Sandya Liyanarachchi

PROVIDER: E-GEOD-3467 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The role of microRNA genes in papillary thyroid carcinoma.

He Huiling H Jazdzewski Krystian K Li Wei W Liyanarachchi Sandya S Nagy Rebecca R Volinia Stefano S Calin George A GA Liu Chang-Gong CG Franssila Kaarle K Suster Saul S Kloos Richard T RT Croce Carlo M CM de la Chapelle Albert A

Proceedings of the National Academy of Sciences of the United States of America 20051219 52

Apart from alterations in the RET/PTC-RAS-BRAF pathway, comparatively little is known about the genetics of papillary thyroid carcinoma (PTC). We show that numerous microRNAs (miRNAs) are transcriptionally up-regulated in PTC tumors compared with unaffected thyroid tissue. A set of five miRNAs, including the three most up-regulated ones (miR-221, -222, and -146), distinguished unequivocally between PTC and normal thyroid. Additionally, miR-221 was up-regulated in unaffected thyroid tissue in sev ...[more]

PMID: 16365291

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Project 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.

Dataset Information

Transcription profiling of micro-RNA genes in human papillary thyroid carcinoma

Publications

The role of microRNA genes in papillary thyroid carcinoma.

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