Oncogenomic and Epigenetic Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
IUBMB Life. 2023 Jan;75(1):30-39. doi: 10.1002/iub.2620. Epub 2022 May 10.
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.
肿瘤中正常静止血管向血管生成的转变是由多种生长因子诱导的，这些生长因子在缺氧和营养物质剥夺时，由癌细胞和基质细胞释放。血管内皮生长因子 A（VEGF-A）是一种有效的分泌有丝分裂原，也是唯一一种特异性作用于内皮细胞的生长因子，几乎在所有血管生成部位都有观察到。癌细胞中 VEGF-A 的表达受到转录和转录后机制的控制。VEGF-A 的转录后调控发生在多个水平，通过控制剪接、mRNA 稳定性和翻译率，实现了 VEGF-A 的精细表达和释放。越来越多的证据强调了 microRNAs（miRNAs）在控制癌症中 VEGF-A mRNA 稳定性和翻译中的重要作用。此外，非编码 RNA，如长非编码 RNA 和环状 RNA，作为 VEGF-A 靶向 miRNAs 的关键调节剂而出现，从而能够调节 VEGF-A 的表达。这篇综述讨论了控制癌细胞中 VEGF-A 表达的 ncRNA 相关网络的最新进展，并深入了解了 VEGF-A 转录后调控的复杂性。
