An oncomir (also oncomiR) is a microRNA (miRNA) that is associated with cancer. MicroRNAs are short RNA molecules about 22 nucleotides in length. Essentially, miRNAs specifically target certain messenger RNAs (mRNAs) to prevent them from coding for a specific protein. The dysregulation of certain microRNAs (oncomirs) has been associated with specific cancer forming (oncogenic) events. Many different oncomirs have been identified in numerous types of human cancers.[1]
Oncomirs are associated with carcinogenesis, malignant transformation, and metastasis. Some oncomir genes are oncogenes, in that overexpression of the gene leads to cancerous growth. Other oncomir genes are tumor suppressors in a normal cell, so that underexpression of the gene leads to cancerous growth.[1][2][3][4]
General mechanism
Oncomirs cause cancer by down-regulating genes by both translational repression and mRNA destabilization mechanisms.[3] These down-regulated genes may code for proteins that regulate the cell's life cycle.
Oncomirs may be at increased or decreased levels within cancerous tissue. In the case of increased oncomir activity, the oncomir is likely suppressing a tumor suppressor gene. In cases of underexpressed oncomirs, regulation is attenuated, allowing the cell to proliferate freely.[5]
Viruses have also been found to have miRNA that mimic parts of natural regulatory human miRNA's. One example is the Epstein–Barr virus (EBV) which is associated with various types of cancer.[5]
History
The first link between miRNA and the growth of cancer was reported in 2002 when researchers observed a down-regulation of miR-15a and miR-16-1 in B-cell chronic lymphocytic leukemia patients.[6] The term is a portmanteau, derived from "oncogenic" + "miRNA", coined by Scott M. Hammond in a 2006 paper characterizing OncomiR-1.[1]
Oncomir addiction
Certain tumors may be "addicted" to oncomirs, meaning that in order to remain tumors, a constant concentration of oncomirs must be present. This is demonstrated by inactivation of the oncomir miR-21. Mice expressing miR-21 contracted pre-B malignant lymphoid-like phenotype tumors. After inactivation of miR-21, the tumors completely regressed.[2] This addiction is part of a more general phenomenon involving oncogenes, called oncogene addiction.[7]
Potential clinical uses of miRNA
Studies have been performed to evaluate the effectiveness of miRNAs as potential markers for cancers. MicroRNAs have shown promise in this area due to their stability and specificity to cells and tumors. A recent study investigated the use of miRNA as a biomarker in pancreatic ductal adenocarcinoma, a form of pancreatic cancer. The study analyzed RNA from biopsied pancreatic cysts to identify deviations in expression of miRNAs. The study found that 228 miRNAs were expressed differently relative to normal pancreatic cells. Included in the findings was an association between hepatocellular carcinoma and the upregulation of miR-92a, a member of OncomiR-1.[8]
Extracellular microRNAs (exRNAs) may also be useful in clinical cancer detection. For example, in a study of cancer patients with a type of lymphoma called diffuse large B-cell lymphoma (DLBCL), serum levels of three miRNA's, miR-21, miR-155 and miR-210, were higher in cancer patients than in healthy controls. In particular, patients with high expression of miR-21 were more apt to have a relapse-free survival.[9] (A table listing cancer type and the associated exRNA biomarker candidates can be found in Kosaka et al..[10])
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