ECE2013 Oral Communications Thyroid (6 abstracts)
Targeting of PATZ1 by miR-29b is a downstream effect of oncogenic Ras signalling in thyroid cells
Michela Vitiello 1, , Teresa Valentino 1, , Marta De Menna 2 , Luigia Serpico 1 , Sonia Mansueto 1 , Gabriella De Vita 2 , Alfredo Fusco 1, & Monica Fedele 1
1Istituto di Endocrinologia ed Oncologia Sperimentale del CNR, Naples, Italy; 2Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università degli Studi di Napoli “Federico II”, Naples, Italy.
PATZ1, a member of the POZ-ZF protein family of transcription factors is emerging as an important cancer-associated factor that can act either as oncogene or tumour-suppressor depending on the cellular context. Consistent with a tumour-suppressor role in thyroid cells, we have shown that PATZ1 is highly downregulated in anaplastic thyroid carcinomas compared to normal thyroid tissue and is a powerful inhibitor of anaplastic thyroid cancer cell survival, migration, invasiveness and tumorigenicity.
Looking for the upstream signalling pathway regulating PATZ1 expression in thyroid cells, we searched for microRNAs targeting PATZ1. In order to identify miRNAs predicted to bind the 3′UTR of PATZ1 we used bioinformatics free tools, based on the miRanda application and the mirSVR predicted target site scoring method. Among the miRNAs identified by this analysis we validated miR-29b. Indeed, we demonstrated that it is able to target PATZ1 and cause downregulation of PATZ1 expression at both mRNA and protein level in different cell systems, including rat thyroid cells. Interestingly, miR-29b is induced by Ras during transformation of FRTL-5 rat thyroid cells toward an undifferentiated phenotype, resembling that of anaplastic carcinomas and characterized by the acquisition of a migratory and invasive behaviour. In these cells, we observed a strong down-regulation of PATZ1 expression, which starts as early as 2 h after Ras induction, and an inverse correlation between the expression of miR-29b and PATZ1 mRNA and protein levels.
These results are consistent with the suppressor role of PATZ in thyroid carcinogenesis and suggest that down-regulation of PATZ1 expression, through miR-29b, may be a downstream effect of the oncogenic Ras signalling in thyroid cell transformation.
Volume 32
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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