The Long Non-Coding RNA RP5-1024C24.1 and Its Associated-Gene MPPED2 Are Down-Regulated in Human Thyroid Neoplasias and Act as Tumour Suppressors

长链非编码 RNA RP5-1024C24.1 及其相关基因 MPPED2 在人类甲状腺肿瘤中下调并发挥肿瘤抑制作用

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作者:Romina Sepe, Simona Pellecchia, Pierre Serra, Daniela D'Angelo, Antonella Federico, Maddalena Raia, Ricardo Cortez Cardoso Penha, Myriam Decaussin-Petrucci, Luigi Del Vecchio, Alfredo Fusco, Pierlorenzo Pallante

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

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.

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.

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