New non-coding RNAs regulate blood vessel formation

Researchers at the University of Eastern Finland have discovered previously unknown non-coding RNAs (ncRNAs) involved in the regulation of gene expression of vascular endothelial growth factors (VEGF), the main regulators of angiogenesis. The study, led by the research groups of Associate Professor Minna Kaikkonen-Määttä and Academy Professor Seppo Ylä-Herttuala, provides a better understanding of the complex interaction of nRNAs with gene regulation, which could open new therapeutic approaches in the future. The results were published in the Molecular and Cellular Biology Journal.

In recent years, the development of next-generation sequencing techniques has revealed that approximately 97% of the human transcriptome is transcribed as non-coding RNA, and although the role of the vast majority remains uncharacterized, many functions such as gene regulation have been proven. .

On the other hand, the endothelial growth factors VEGF-A and VEGF-C are the main regulator of angiogenesis, that is, the formation of new blood vessels. Due to their important role in the development of the vascular system, they are a potential target for the treatment of several diseases, such as atherosclerosis. Therapeutic angiogenesis has been developed as a promising strategy to save ischemic tissue by inducing new blood vessels sprouting from an existing vascular system, but so far very little of clinical significance has been obtained. . Therefore, a more in-depth understanding of the regulatory mechanisms underlying the expression of these key angiogenic factors is needed for future therapeutic avenues.

In this study, researchers performed an in-depth characterization of the genomic loci around the VEGFA and VEGFC genes and identified new non-coding RNAs, in particular enhancer RNAs (eRNAs) and long non-coding RNAs (lncRNAs). While enhancers clearly upregulated gene expression, lncRNAs demonstrated various functions. Interestingly, lncRNAs also regulated other targets, including factors related to endothelial functions, such as angiogenesis and cell proliferation.

Reference: Mushimiyimana I, Tomas Bosch V, Niskanen H et al. Genomic landscapes of non-coding RNAs regulating the expression of VEGFA and VEGFC in endothelial cells. Mol Cell Biol. 2021. doi: 10.1128 / MCB.00594-20

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