Abstract
Long non-coding RNAs (lncRNAs) are important for transcription and for epigenetic or posttranscriptional regulation of gene expression and may contribute to carcinogenesis. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), an lncRNA involved in the regulation of the cell cycle, cell proliferation, and cell migration, is known to be deregulated in multiple cancers. Here, we analyzed the expression of MALAT1 on 195 cases of benign and malignant thyroid neoplasms by using tissue microarrays for RNA in situ hybridization (ISH) and real-time PCR. MALAT1 is highly expressed in normal thyroid (NT) tissues and thyroid tumors, with increased expression during progression from NT to papillary thyroid carcinomas (PTCs) but is downregulated in poorly differentiated thyroid cancers (PDCs) and anaplastic thyroid carcinomas (ATCs) compared to NT. Induction of epithelial to mesenchymal transition (EMT) by transforming growth factor (TGF)-beta in a PTC cell line (TPC1) led to increased MALAT1 expression, supporting a role for MALAT1 in EMT in thyroid tumors. This is the first ISH study of MALAT1 expression in thyroid tissues. It also provides the first piece of evidence suggesting MALAT1 downregulation in certain thyroid malignancies. Our findings support the notion that ATCs may be molecularly distinct from low-grade thyroid malignancies and suggest that MALAT1 may function both as an oncogene and as a tumor suppressor in different types of thyroid tumors.
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Acknowledgments
We kindly thank Dr. Daniel T. Ruan (Brigham and Women’s Hospital, Boston, MA) for the TPC1 cell line and the staffs of the Translational Research in Pathology (TRIP) (University of Wisconsin Carbone Cancer Center Cancer Center Support Grant P30 CA014520) for their services. Dr. Ranran Zhang received a research grant from the Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health.
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The study was approved by the Institutional Review Board at the University of Wisconsin–Madison.
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Presented as a Poster Session at the 105th Meeting of the US and Canadian Academy of Pathology in Seattle, WA, 2016.
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Zhang, R., Hardin, H., Huang, W. et al. MALAT1 Long Non-coding RNA Expression in Thyroid Tissues: Analysis by In Situ Hybridization and Real-Time PCR. Endocr Pathol 28, 7–12 (2017). https://doi.org/10.1007/s12022-016-9453-4
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DOI: https://doi.org/10.1007/s12022-016-9453-4