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Non-coding RNA regulatory networks in post-transcriptional regulation of VEGFA in cancer.

ABSTRACT: The switch from the normal quiescent vasculature to angiogenesis in tumors is induced by a variety of growth factors, released from cancer and stromal cells upon oxygen and nutrients deprivation. Vascular endothelial growth factor A (VEGF-A) is a potent-secreted mitogen and the only growth factor specific to endothelial cells that is observed almost ubiquitously at sites of angiogenesis. Expression of VEGF-A in cancer cells is controlled through transcriptional and post-transcriptional mechanisms. Post-transcriptional regulation of VEGF-A occurs at multiple levels, through the control of splicing, mRNA stability and translation rate, enabling a fine-tuned expression and release of VEGF-A. Mounting evidence is highlighting the important role played by microRNAs (miRNAs) in the control of VEGF-A mRNA stability and translation in cancer. Moreover, non-coding RNAs, as long non-coding RNAs and circular RNAs, are emerging as crucial modulators of VEGF-A-targeting miRNAs, with consequent ability to modulate VEGF-A expression. This review discusses the recent progress on the ncRNA-related networks controlling VEGF-A expression in cancer cells and provides insights into the complexity of VEGF-A post-transcriptional regulation.

SUBMITTER: Fontemaggi G

PROVIDER: S-EPMC10084289 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Non-coding RNA regulatory networks in post-transcriptional regulation of VEGFA in cancer.

Fontemaggi Giulia G

IUBMB life 20220510 1

The switch from the normal quiescent vasculature to angiogenesis in tumors is induced by a variety of growth factors, released from cancer and stromal cells upon oxygen and nutrients deprivation. Vascular endothelial growth factor A (VEGF-A) is a potent-secreted mitogen and the only growth factor specific to endothelial cells that is observed almost ubiquitously at sites of angiogenesis. Expression of VEGF-A in cancer cells is controlled through transcriptional and post-transcriptional mechanism ...[more]

PMID: 35467790

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Project description:BackgroundTranscriptional regulation is a fundamental process in biological systems, where transcription factors (TFs) have been revealed to play crucial roles. In recent years, in addition to TFs, an increasing number of non-coding RNAs (ncRNAs) have been shown to mediate post-transcriptional processes and regulate many critical pathways in both prokaryotes and eukaryotes. On the other hand, with more and more high-throughput biological data becoming available, it is possible and imperative to quantitatively study gene regulation in a systematic and detailed manner.ResultsMost existing studies for inferring transcriptional regulatory interactions and the activity of TFs ignore the possible post-transcriptional effects of ncRNAs. In this work, we propose a novel framework to infer the activity of regulators including both TFs and ncRNAs by exploring the expression profiles of target genes and (post)transcriptional regulatory relationships. We model the integrated regulatory system by a set of biochemical reactions which lead to a log-bilinear problem. The inference process is achieved by an iterative algorithm, in which two linear programming models are efficiently solved. In contrast to available related studies, the effects of ncRNAs on transcription process are considered in this work, and thus more reasonable and accurate reconstruction can be expected. In addition, the approach is suitable for large-scale problems from the viewpoint of computation. Experiments on two synthesized data sets and a model system of Escherichia coli (E. coli) carbon source transition from glucose to acetate illustrate the effectiveness of our model and algorithm.ConclusionOur results show that incorporating the post-transcriptional regulation of ncRNAs into system model can mine the hidden effects from the regulation activity of TFs in transcription processes and thus can uncover the biological mechanisms in gene regulation in a more accurate manner. The software for the algorithm in this paper is available upon request.

Dataset Information

Non-coding RNA regulatory networks in post-transcriptional regulation of VEGFA in cancer.

Publications

Non-coding RNA regulatory networks in post-transcriptional regulation of VEGFA in cancer.

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