Abstract
Background: Well-differentiated papillary thyroid carcinoma (PTC) represents the thyroid neoplasia with the highest incidence. Long non-coding RNAs (lncRNAs) have been found deregulated in several human carcinomas, and hence, proposed as potential diagnostic and prognostic markers. Therefore, the aim of our study was to investigate their role in thyroid carcinogenesis. Methods: We analysed the lncRNA expression profile of 12 PTC and four normal thyroid tissues through a lncRNA microarray. Results: We identified 669 up- and 2470 down-regulated lncRNAs with a fold change >2. Among them, we focused on the down-regulated RP5-1024C24.1 located in an antisense position with respect to the MPPED2 gene which codes for a metallophosphoesterase with tumour suppressor activity. Both these genes are down-regulated in benign and malignant thyroid neoplasias. The restoration of RP5-1024C24.1 expression in thyroid carcinoma cell lines reduced cell proliferation and migration by modulating the PTEN/Akt pathway. Inhibition of thyroid carcinoma cell growth and cell migration ability was also achieved by the MPPED2 restoration. Interestingly, RP5-1024C24.1 over-expression is able to increase MPPED2 expression. Conclusions: Taken together, these results demonstrate that RP5-1024C24.1 and MPPED2 might be considered as novel tumour suppressor genes whose loss of expression contributes to thyroid carcinogenesis.
Highlights
Thyroid carcinomas are moderately rare, constituting 1% of all human carcinomas, but represent the highest percentage of all malignancies derived from the endocrine system [1]
Cancers 2018, 10, 146 from thyroid follicular cells consist of a wide spectrum of lesions with increasing degree of malignancies going from benign follicular thyroid adenomas (FTA), to differentiated carcinomas, to completely undifferentiated carcinomas that are always fatal [2]
In order to identify the Long non-coding RNAs (lncRNAs) deregulated in papillary thyroid carcinoma (PTC), we analysed the lncRNA expression profile of 12 PTC and four normal thyroid tissues by hybridizing the RNA extracted from these samples to the Human LncRNA Microarray Version 3.0 (Arraystar, Rockville, MD, USA)
Summary
Thyroid carcinomas are moderately rare, constituting 1% of all human carcinomas, but represent the highest percentage of all malignancies derived from the endocrine system [1]. Cancers 2018, 10, 146 from thyroid follicular cells consist of a wide spectrum of lesions with increasing degree of malignancies going from benign follicular thyroid adenomas (FTA), to differentiated carcinomas (papillary thyroid carcinomas, PTC, and follicular thyroid carcinomas, FTC), to completely undifferentiated carcinomas (anaplastic thyroid carcinomas, ATC) that are always fatal [2]. PTC is the most frequent histotype representing about 80% of all diagnosed thyroid carcinomas. MicroRNA (miRNA) deregulated expression has been frequently described in human thyroid carcinomas [10]. Well-differentiated papillary thyroid carcinoma (PTC) represents the thyroid neoplasia with the highest incidence. Long non-coding RNAs (lncRNAs) have been found deregulated in several human carcinomas, and proposed as potential diagnostic and prognostic markers. The aim of our study was to investigate their role in thyroid carcinogenesis
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