Long Non-Coding RNA MALAT1 Expression in Thyroid Tissues and Tumors

Background: Long non-coding RNAs (lncRNAs) participate in transcription and in epigenetic or post-transcriptional regulation of gene expression, and may contribute to carcinogenesis. MALAT1 (Metastasis Associated Lung Adenocarcinoma Transcript 1), a lncRNA that participates in the regulation of cell cycle and migration, is known to be deregulated in multiple cancers. Some studies suggest MALAT1 may function as both an oncogene and a tumor suppressor. We analyzed the expression of the MALAT1in thyroid tumors and compared its expression to miR-146b-5p, a microRNA known to be deregulated in papillary thyroid cancer. Design: Tissue microarrays (TMAs) were constructed with formalin-fixed paraffin-embedded (FFPE) tissues of normal thyroid ( NT, n=10), nodular goiters (NG, n=10), follicular adenoma (FA, n=32), follicular carcinoma (FCA, n=28), papillary thyroid carcinoma ( PTC n=28), follicular variant of papillary thyroid carcinoma( FVPTC, n=29), poorly differentiated thyroid carcinomas (PDC, n=21) and anaplastic thyroid carcinoma (ATC, n=35). TMA sections were analyzed by in situ hybridization (ISH) using RNAscope technology with a MALAT1 probe (Advanced Cell Diagnostics). ISH for miR-146b-5p was also performed on the same set of TMAs (Exiqon). qRT-PCR was performed on a subset of the TMA cases (n=16). The results of the MALAT1 TMA ISH were analyzed with Vectra imaging technology, Nuance® and inForm ® software. Results: MALAT1 was highly expressed in NT, NG and in benign and malignant thyroid tumors predominantly in the nucleus, but also in the cytoplasm. The highest levels of MALAT1 wwere observed in PTCs which was significantly higher than in NT (p=0.014) and FVPTC (p=0.016). In contrast NT expressed higher levels of MALAT1 than PDC (p=0.015) or ATC (p