Causes And Consequences Of MicroRNA Dysregulation In Cancer

Carlo M. Croce, M.D.

Abstract

As miRNAs have multiple targets, their function in tumorigenesis could be due to their regulation of a few specific tar⁃gets, possibly even one, or many targets. A future challenge will be to identify all ofthe targets of the miRNAs involved inCancerand establish their contribution to malignant transformation. An additional challenge will be the identification of all of the miRNAs that are dysregulated by path⁃ways that are consistently dysregulated invarious 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 antimiRNAs 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 chemo⁃therapy to targeted therapies, and miRNAsand anti-miRNAs will contribute exten⁃sively to the latter.

Background

Dr. Carlo M. Croce’s paper whichpublished in 2002 reported that chroniclymphocytic leukemia (CLL), the most common human leukemia, appears to be caused by the loss of two miRNA genes. As a consequence of this revolutionary discovery and his following researches on miRNA, Dr. Croce leads the pursuit of miRNAs as fundamental players in the cancer process.

According to Dr. Croce’ s researches, miRNA dysfunction can cause many dis⁃eases including cancer. As a consequence, these miRNA can certainly be used for cancer diagnostics and prognostics. With the better understanding of the diseases, it⁃will be possible to use miRNA or antimiRNA to go in and perhaps reverse or alter the disease process. (Edited by Yichu Ye).