Frontiers in Microbiology · 2018 · 17 citations · 78 references
MedicineMolecular BiologyOncologyCarcinogenesisGene ExpressionMolecular OncologyBladder CancerCancer ProgressionUrothelial CarcinomaApobec EnzymesApobec Mutation SignaturesCarcinogenic PathwaysMechanisms Of CarcinogenicityMutational Signature AnalysisUrothelial Carcinoma Predisposition
. While we observed evidence suggesting that L1 expression has a weak positive effect on A3B and A3G expression and A3B promoter activity, neither efficient siRNA-mediated knockdown nor overexpression of functional L1 elements affected catalytic activity of A3 proteins consistently. However, L1 knockdown diminished proliferation of a UC cell line exhibiting robust endogenous L1 expression, but had little impact on a cell line with low L1 expression levels. Our results indicate that UC cells express A3B at levels exceeding A3A levels by far, making A3B the prime candidate for causing genomic mutations. Our data provide evidence that L1 activation constitutes only a minor and negligible factor involved in induction or upregulation of endogenous A3 expression in UC.
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