Towards an extension of the two-variable model of carcinogenesis through oncogenes and tumour suppressor genes

Currently, carcinogenesis is considered to be the result of mal-expression of tumour suppressor genes and oncogenes, leading either way to uncontrollable and disorganized cell mitosis. Recently a novel class of genes has drawn the interest of the scientific community. These are microRNAs (miRNAs), a class of noncoding RNAs, 20-23 nucleotides in length, that can up or downregulate gene expression of downstream gene targets (including transcription factors, oncogenes, and tumour suppressor genes) at the post-transcriptional level. Some members of this new class of genes seem to have the potential to act simultaneously either as oncogenes or as tumour suppressor genes depending on the molecular micro-environment of the cell. We elaborate on this hypothesis by giving examples of miRNAs (e.g. mir-9, miR-17-92) which seem to function by the abovementioned mechanism. This could mean that the deterministic notion of carcinogenesis as a result of merely tumour suppressor genes and oncogenes deregulation could be revised to contain the fact that certain members of this novel class of genes have the potential to play both roles simultaneously. (C) 2011 Elsevier Ltd. All rights reserved.