Integrated characterization of MicroRNA and mRNA transcriptome in papillary thyroid carcinoma

Azliana Mohamad Yusof, A. Rahman A. Jamal, Rohaizak Muhammad, Shahrun Niza Abdullah Suhaimi, Isa Mohamed Rose, Sazuita Saidin, Nurul Syakima Ab Mutalib

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article number158
JournalFrontiers in Endocrinology
Volume9
Issue numberAPR
DOIs
Publication statusPublished - 16 Apr 2018

Fingerprint

MicroRNAs
Transcriptome
Messenger RNA
Lymph Nodes
Neoplasm Metastasis
Papillary Thyroid cancer
Genes
Mutation
Biomarkers
RNA Sequence Analysis
Ribosomal RNA
Gene Regulatory Networks
Tumor Biomarkers
Computational Biology
Neoplasms
Carcinogenesis

Keywords

  • BRAF V600E
  • Integrated analyses
  • MicroRNA
  • Papillary thyroid carcinoma
  • Transcriptome sequencing

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Integrated characterization of MicroRNA and mRNA transcriptome in papillary thyroid carcinoma. / Yusof, Azliana Mohamad; A. Jamal, A. Rahman; Muhammad, Rohaizak; Abdullah Suhaimi, Shahrun Niza; Rose, Isa Mohamed; Saidin, Sazuita; Ab Mutalib, Nurul Syakima.

In: Frontiers in Endocrinology, Vol. 9, No. APR, 158, 16.04.2018.

Research output: Contribution to journalArticle

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