MicroRNA Involvement in Human Cancers

Recent evidence has revealed that microRNAs (miRNAs) function as tumor suppressors and oncogenes, and therefore miRNAs might prove useful in the diagnosis and treatment of cancer. In 2002, Croce's group reported the first connection between miRNAs and cancer, showing that the MIR15A(4) (microRNA 15a) and MIR16-1 (microRNA 16-1) genes were deleted and/or downregulated in the majority of B-cell lymphomas (1). The findings that miRNAs were frequently located at cancer-associated genomic regions, including fragile sites, prompted these investigators to propose that miRNA genes were a new class of genes involved in human tumorigenesis (2). The development of miRNA gene expression profiling allowed the identification of miRNA gene expression signatures unique to specific solid tumors (e. g., lung, breast, stomach, prostate, and colon) and their cellular origins (3). These reports indicated the extensive involvement of miRNAs in the pathogenesis of solid cancer and highlighted their potential as biomarkers for cancer. Additional studies have shown a strong correlation between impaired expression of miRNA genes and oncogenesis (4). For example, the RAS oncogenes are regulated by the let-7 family of miRNAs, and MIR155 and MIR gene clusters 17-92 are associated with the MYC [v-myc myelocytomatosis viral oncogene homolog (avian)] oncogene. These findings suggest that miRNAs play a substantial role in the pathogenesis of human cancers.