Causes and consequences of microRNA dysregulation in cancer

Abstract

This paper describes the alterations and mechanisms that are involved in microRNA (miRNA) dysregulation in human cancer and how such dysregulation is involved in cancer initiation and progression. miRNA profiling can be used to assess which miRNAs are dysregulated in human cancer. miRNAs acting as tumour suppressors target important oncogenes, such as B cell leukaemia/lymphoma 2 (BCL2), MYC and RAS. miRNAs acting as oncogenes target important tumour suppressors, such as phosphatase and tensin homologue (PTEN), p27, p57 and tissue inhibitor of metalloproteinases 3 (TIMP3). miRNA genes can be silenced by epigenetic changes and can cause epigenetic changes that result in the silencing of tumour suppressor genes; for example, loss of miR-29 family members results in the overexpression of DNA methyltransferases and the silencing of tumour suppressors. Reintroduction of miR-29 family members into tumour cells that have lost them results in the reactivation of silenced tumour suppressors and the suppression of tumorigenicity. The same miRNAs are dysregulated in multiple human tumours, which suggests that they may be downstream targets of pathways that are commonly dysregulated in human cancer. Dysregulated miRNAs could be targets for anticancer treatment.