Abstract
RNA polymerase (pol) III transcription is responsible for the transcription of small, untranslated RNAs involved in fundamental metabolic processes such mRNA processing (U6 snRNA) and translation (tRNAs). RNA pol III transcription contributes to the regulation of the biosynthetic capacity of a cell and a direct link exists between cancer cell proliferation and deregulation of RNA pol III transcription. Accurate transcription by RNA pol III requires TFIIIB, a known target of regulation by oncogenes and tumor suppressors. There have been significant advances in our understanding of how TFIIIB-mediated transcription is deregulated in a variety of cancers. Recently, BRF2, a component of TFIIIB required for gene external RNA pol III transcription, was identified as an oncogene in squamous cell carcinomas of the lung through integrative genomic analysis. In this review, we focus on recent advances demonstrating how BRF2-TFIIIB mediated transcription is regulated by tumor suppressors and oncogenes. Additionally, we present novel data further confirming the role of BRF2 as an oncogene, extracted from the Oncomine database, a cancer microarray database containing datasets derived from patient samples, providing evidence that BRF2 has the potential to be used as a biomarker for patients at risk for metastasis. This data further supports the idea that BRF2 may serve as a potential therapeutic target in a variety of cancers.
Highlights
Cancer is a major health problem afflicting millions of Americans annually and despite tremendous research and treatment advances, is still the leading cause of death amongst men and women younger than age 85 years [1]
RNA polymerase III contains the largest number of subunits (17 subunits) and is responsible for the transcription of small, less than 300 nucleotides, untranslated RNAs involved in fundamental metabolic processes, such as RNA processing (U6 snRNA) and translation, which contribute to cell proliferation [2]
Lockwood et al identified BRF2 as a novel oncogene in lung squamous cell carcinoma demonstrating that overexpression of BRF2 can drive expression of RNA pol III transcripts contributing to squamous cell carcinoma tumorigenesis [20]
Summary
Cancer is a major health problem afflicting millions of Americans annually and despite tremendous research and treatment advances, is still the leading cause of death amongst men and women younger than age 85 years [1]. Lockwood et al identified BRF2 as a novel oncogene in lung squamous cell carcinoma demonstrating that overexpression of BRF2 can drive expression of RNA pol III transcripts contributing to squamous cell carcinoma tumorigenesis [20]. The 4 analyses which are significant out of 162 that are significant include gastric, kidney and melanoma cancer datasets (Figure 3) This criterion for this specific BRF2 disease summary performed was stringent as we required a p-value of 1E-4 and a fold-change of 2 for BRF2 gene expression compared to the controls. Analysis of the 95% outlier across 17 breast carcinoma analyses (Figure 6) shows that BRF2 is highly overexpressed This demonstrates that in 5% of the samples analyzed in these specific studies, BRF2 overexpression is significant in a small subpopulation of samples. This study is in its infancy, it’s representative of the potential use of RNA pol III inhibitors as a means of pharmacological target for the treatment of cancers
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