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, Alfredo Fusco

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)8341-8354
Number of pages14
JournalOncotarget
Volume5
Issue number18
Publication statusPublished - 2014

Keywords

  • ceRNA
  • HMGA1
  • HMGA1P6
  • HMGA1P7
  • miRNA

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

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  • Cite this

    Esposito, F., de Martino, M., Petti, M. G., Forzati, F., Tornincasa, M., Federico, A., Arra, C., Pierantoni, G. M., & Fusco, A. (2014). HMGA1 pseudogenes as candidate proto-oncogenic competitive endogenous RNAs. Oncotarget, 5(18), 8341-8354.