Oncotarget

Research Papers:

HMGA1 pseudogenes as candidate proto-oncogenic competitive endogenous RNAs

Francesco Esposito _, Marco De Martino, Maria Grazia Petti, Floriana Forzati, Mara Tornincasa, Antonella Federico, Claudio Arra, Giovanna Maria Pierantoni and Alfredo Fusco

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Oncotarget. 2014; 5:8341-8354. https://doi.org/10.18632/oncotarget.2202

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Abstract

Francesco Esposito1, Marco De Martino1, Maria Grazia Petti1, Floriana Forzati1, Mara Tornincasa1, Antonella Federico1, Claudio Arra2, Giovanna Maria Pierantoni1, Alfredo Fusco1

1 Istituto di Endocrinologia ed Oncologia Sperimentale del CNR c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Scuola di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli “Federico II”, Naples, Italy.

2 Istituto Nazionale dei Tumori, Fondazione Pascale, Naples, Italy.

Correspondence to:

Dr. Alfredo Fusco, e-mail: alfusco@unina.it

Key words: HMGA1P6, HMGA1P7, HMGA1, ceRNA, miRNA

Received: May 06, 2014     Accepted: July 08, 2014     Published: July 15, 2014

ABSTRACT

The High Mobility Group A (HMGA) are nuclear proteins that participate in the organization of nucleoprotein complexes involved in chromatin structure, replication and gene transcription. HMGA overexpression is a feature of human cancer and plays a causal role in cell transformation. Since non-coding RNAs and pseudogenes are now recognized to be important in physiology and disease, we investigated HMGA1 pseudogenes in cancer settings using bioinformatics analysis. Here we report the identification and characterization of two HMGA1 non-coding pseudogenes, HMGA1P6 and HMGA1P7. We show that their overexpression increases the levels of HMGA1 and other cancer-related proteins by inhibiting the suppression of their synthesis mediated by microRNAs. Consistently, embryonic fibroblasts from HMGA1P7-overexpressing transgenic mice displayed a higher growth rate and reduced susceptibility to senescence. Moreover, HMGA1P6 and HMGA1P7 were overexpressed in human anaplastic thyroid carcinomas, which are highly aggressive, but not in differentiated papillary carcinomas, which are less aggressive. Lastly, the expression of the HMGA1 pseudogenes was significantly correlated with HMGA1 protein levels thereby implicating HMGA1P overexpression in cancer progression. In conclusion, HMGA1P6 and HMGA1P7 are potential proto-oncogenic competitive endogenous RNAs.


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