Abstract
Since the discovery of miR-15a and miR-16-1 deletions in CLL15, many laboratories around the world have shown miRNA dysregulation in all tumors studied, including the most common, such as lung, breast, prostate and gastrointestinal cancers. Such dysregulation, like the dysregulation of oncogenes and tumor suppressor genes, can be caused by multiple mechanisms, such as deletion, amplification, mutation, transcriptional dysregulation and epigenetic changes.
As miRNAs have multiple targets, their function in tumorigenesis could be due to their regulation of a few specific targets, possibly even one, or many targets. A future challenge will be to identify all of the targets of the miRNAs involved in cancer and establish their contribution to malignant transformation. An additional challenge will be the identification of all of the miRNAs that are dysregulated by pathways that are consistently dysregulated in various types of human cancers. This point is of particular importance, as instead of focusing on specific alterations in protein-coding oncogenes or tumor suppressor genes — which may be difficult to treat — we could focus on their downstream miRNA targets. If these miRNA targets are crucial for the expression of the malignant phenotype and the cancer cells depend on their dysregulation for proliferation and survival, we can expect that the use of miRNAs or anti-miRNAs will result in tumor regression. Genomic analyses for alteration in miRNA genes or for copy number alterations in various human tumors by deep sequencing is in progress but has not been completed. These studies could provide additional information concerning the involvements of miRNAs in cancer and in many other diseases.
Over the past few years, we have observed a shift from conventional chemotherapy to targeted therapies, and miRNAs and anti-miRNAs will contribute extensively to the latter.
Citation Format: Carlo M. Croce. microRNAs and cancer progression. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr ED06-02.
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