Patterns of microRNA Expression in Non-Human Primate Cells Correlate with Neoplastic Development In Vitro

Neoplastic development represents cumulative genetic and epigenetic events leading to the emergence of cells that can attain a tumorigenic phenotype. Neoplastic transformation of cells cultured in vitro can be induced by several methods, such as treatment with chemical carcinogens or radiation, viral infection, or the introduction of oncogenes. To help understand how tumors originate and progress in mammals, cells transformed in vitro by these methods have been used for many years to study processes analogous to neoplastic development in vivo.

To identify miRNA signatures associated with different stages of neoplastic development, the authors used custom microarrays containing primate miRNAs to examine the expression profile in VERO cells (a neoplastically transformed cell line being used for the manufacture of viral vaccines), progenitor primary African green monkey kidney (pAGMK) cells, and several VERO cell derivatives. Because the genome sequence of the African green monkey is not available, there are no commercially available miRNA arrays specific to the African green monkey. Therefore, a custom primate miRNA microarray that contained all human and non-human primate miRNA transcripts (776 miRs from 11 species, miRBase V10) was used.

They identified 10 up-regulated miRNAs whose level of expression correlated with VERO cell evolution from a non-tumorigenic phenotype to a tumorigenic phenotype. The overexpression of the polycistronic cluster of miR-376a, miR-376b and miR-376c conferred phenotypic changes to the non-tumorigenic cells.

The associations between neoplastic processes and miRNA dysregulation in the VERO-cell model presented in this report provide additional support for the concept that neoplastic development in vitro and in vivo have similarities. If further evidence for these similarities is forthcoming, the VERO-cell model may provide a format for the systematic comparison of neoplastic development in vivo and neoplastic transformation in vitro across tissues, organs, and species.

Teferedegne B, Murata H, Quiñones M, Peden K, Lewis AM Jr (2010) Patterns of microRNA Expression in Non-Human Primate Cells Correlate with Neoplastic Development In Vitro. PLoS ONE 5(12), e14416. [article]