Small ribonucleic acid (RNA) can act as specific regulators of gene expression. Over the years many new small functional RNAs have been found. RNAs are usually thought of as messenger RNA, which serve as templates for the translation of genes into proteins. Encoding of the DNA sequence is often referred to as an RNA gene. Hundreds of genes in our genome encode small functional RNA molecules collectively called microRNAs (miRNAs).
MicroRNAs are a class of non-coding regulatory RNAs, they are approximately 22 nucleotides long, involved in differentiation, development, and metabolism (Castoldi, 2006). Acting at the post-transcriptional level, miRNAs can fine-tune the expression of about 30 percent of mammalian protein-encoding genes.
MicroRNAs (miRNAs) were first discovered by Victor Ambros along with colleagues Roaslind Lee and Rhonda Feinbaum in 1993. Ambros and colleagues conducted a genetic screening of the roundworm Caenorhabditis elegans and identified genes involved in developmental timing (Sassen, 2008). These discoveries along with the discovery of miRNAs in Drosophila were shown to control cell proliferation and apoptosis.
MicroRNAs are shown to control a variety of biological processes, such as cell cycle, apoptosis, and various physiological properties. In addition, highly tissue-specific expression and distinct time-based expression patterns during embryogenesis suggest that microRNAs play a key role in the differentiation and maintenance of tissue identity. MiRNAs have also been implicated in a variety of diseases including various cancers, neurological diseases, and heart disease (Sassen, 2008).
All cancers share a number of characteristics, including an increased ability to proliferate, alterations to the cell cycle, and a loss of cellular identity (Sassen, 2008). Research has shown that miRNAs are able to regulate these processes, suggesting their involvement in cancer development.
In C. elegans, lin-4 and let-7 control the timing of development; mutations in the miRNAs result in abnormalities in the cell cycle along with execution of terminal differentiation program. This prevents the cells from reaching their fully differentiated state. When researchers discovered human microRNAs they noticed that many of the miRNAs were located along fragile sites in the genome or in regions that are commonly amplified or deleted in human cancers (Sassen, 2008). Tumor cell lines and malignant tumors were found to have widespread deregulated miRNA expression compared to normal tissues (Sassen, 2008). Many miRNAs are found to be up- or down-regulated in the cancer samples as they relate to their normal tissue counterparts.
Approximately five years ago miRNAs role in cancer was first reported. Studies show that microRNAs have oncogenic properties, the first was identified was miR-155 (Metzler, 2004). Early studies showed miR-155 to be upregulated in Burkitt’s lymphoma. miR-155 is located on chromosome 21in a host of non-coding RNA called the B cell integration (BIC) and is highly expressed in pediatric Burkitt’s lymphoma. Constinean et al. conducted a study that showed transgenic mice with a pre-B-cell targeted over expression of miR-155. The mice were fertile and viable but developed polyclonal lymphoproliferative disorder which was then followed by pre-B-leukemia. These results provided evidence that if microRNAs are deregulated cancer can develop (Sandhu, 2011).…
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