Dataset Information

In-depth characterization of the microRNA transcriptome in normal thyroid and papillary thyroid carcinoma.

ABSTRACT:

Context

A single microRNA gene may give rise to several mature products that differ in length, called isomiRs. IsomiRs are known to be tissue specific and functionally relevant. The microRNA sequence heterogeneity of the thyroid gland has yet to be determined.

Objective

The objective of the study was to provide a comprehensive view of the microRNA transcriptome in normal thyroid and papillary thyroid carcinoma (PTC).

Design

We used next-generation deep sequencing to analyze microRNA length heterogeneity and expression profiles of PTC tumors (n = 14), unaffected tissue adjacent to tumors (n = 14), and control, noncancerous thyroid tissue (n = 14). The results were validated with a microarray on an additional set of 9 PTC tumor/normal tissue pairs.

Results

Eighty-nine microRNAs were significantly deregulated in PTC compared with normal thyroid tissue (false discovery rate < 0.05, fold change 0.13-20.7). Top deregulated miRNAs included miR-146b-5p, miR-221-3p, miR-7-3p, miR-551b-3p, miR-486-3p, and miR-144-3p, confirming previous microarray profiling. The expression of miRNAs did not depend on the BRAF mutation status. Interestingly, 85% of the most abundant microRNAs consisted of isoforms that differed from the standard reference sequence deposited in miRBase. Moreover, the reference microRNAs were completely absent in 42.4% and 35.9% of the microRNAs expressed in normal thyroid and PTC tumors, respectively. Numerous isomiRs had altered seed sequences, which led to a different set of target genes. For highly deregulated miR-146b-5p, we detected 6 isoforms (tumor/normal fold change 14.4-28.7, false discovery rate < 0.002) that varied at their 5' ends with a 1-nt difference that created 2 alternative seeds. The target genes for those 2 seeds overlapped in only 13.1% of genes.

Conclusions

Almost all microRNAs exhibit isoforms of variable length and potentially distinct function in thyroid tumorigenesis.

SUBMITTER: Swierniak M

PROVIDER: S-EPMC5399477 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Publications

In-depth characterization of the microRNA transcriptome in normal thyroid and papillary thyroid carcinoma.

Swierniak Michal M Wojcicka Anna A Czetwertynska Malgorzata M Stachlewska Elzbieta E Maciag Monika M Wiechno Wieslaw W Gornicka Barbara B Bogdanska Magdalena M Koperski Lukasz L de la Chapelle Albert A Jazdzewski Krystian K

The Journal of clinical endocrinology and metabolism 20130619 8

<h4>Context</h4>A single microRNA gene may give rise to several mature products that differ in length, called isomiRs. IsomiRs are known to be tissue specific and functionally relevant. The microRNA sequence heterogeneity of the thyroid gland has yet to be determined.<h4>Objective</h4>The objective of the study was to provide a comprehensive view of the microRNA transcriptome in normal thyroid and papillary thyroid carcinoma (PTC).<h4>Design</h4>We used next-generation deep sequencing to analyze ...[more]

PMID: 23783103

Similar Datasets

Project description:The incidence rate of papillary thyroid carcinoma (PTC) has rapidly increased in the recent decades, and the microRNA (miRNA) is one of the potential biomarkers in this cancer. Despite good prognosis, certain features such as lymph node metastasis (LNM) and BRAF V600E mutation are associated with a poor outcome. More than 50% of PTC patients present with LNM and BRAF V600E is the most common mutation identified in this cancer. The molecular mechanisms underlying these features are yet to be elucidated. This study aims to elucidate miRNA-genes interaction networks in PTC with or without LNM and to determine the association of BRAF V600E mutation with miRNAs and genes expression profiles. Next generation sequencing was performed to characterize miRNA and gene expression profiles in 20 fresh frozen tumor and the normal adjacent tissues of PTC with LNM positive (PTC LNM-P) and PTC without LNM (PTC LNN). BRAF V600E was genotyped using Sanger sequencing. Bioinformatics integration and pathway analysis were performed to determine the regulatory networks involved. Based on network analysis, we then investigated the association between miRNA and gene biomarkers, and pathway enrichment analysis was performed to study the role of candidate biomarkers. We identified 138 and 43 significantly deregulated miRNAs (adjusted p value?<?0.05; log2 fold change???-1.0 or ?1.0) in PTC LNM-P and PTC LNN compared to adjacent normal tissues, respectively. Ninety-six miRNAs had significant expression ratios of 3p-to-5p in PTC LNM-P as compared to PTC LNN. In addition, ribosomal RNA-reduced RNA sequencing analysis revealed 699 significantly deregulated genes in PTC LNM-P versus normal adjacent tissues, 1,362 genes in PTC LNN versus normal adjacent tissue, and 1,576 genes in PTC LNM-P versus PTC LNN. We provide the evidence of miRNA and gene interactions, which are involved in LNM of papillary thyroid cancer. These findings may lead to better understanding of carcinogenesis and metastasis processes. This study also complements the existing knowledge about deregulated miRNAs in papillary thyroid carcinoma development.

Dataset Information

In-depth characterization of the microRNA transcriptome in normal thyroid and papillary thyroid carcinoma.

Context

Objective

Design

Results

Conclusions

Publications

In-depth characterization of the microRNA transcriptome in normal thyroid and papillary thyroid carcinoma.

Similar Datasets

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