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.