Post-transcriptional regulation of angiogenesis in development and cancer

30/06/2022 – ore 14:00

Abstract:

Alternative splicing (AS) is the molecular process generating multiple mRNAs from a single gene, thus producing different protein isoforms. By affecting gene expression and proteome diversity, AS regulates tissue development, cell differentiation and homeostasis. Altered expression of specific AS regulators leads to the production of AS isoforms involved in neoplastic transformation, cancer progression or resistance to therapeutic treatments. Given that many AS variants are cancer-specific, they are particularly relevant for the diagnosis, prognosis, and targeted cancer therapy.
The role of aberrant AS regulation in tumor angiogenesis has begun to be revealed only recently. In this regard, we showed that Nova2, a splicing factor previously considered neural cell-specific, is also expressed in endothelial cells (ECs) of different human tissues, but not other cell types within the tissue. By combining in vivo and in vitro loss-of-function with genome-wide approaches, we found that Nova2 is crucial for vascular development. Moreover, we identified novel transcripts regulated by Nova2-mediated AS in ECs and we characterized the vascular role of several of them.
During my talk, I will summarize our recent results showing that Nova2 has a prognostic value in cancer, is required for tumor angiogenesis and tumor growth, and that Nova2 and Nova2-mediated AS play a relevant role in the phenotypic and functional aberrancies of cancer blood vessels.

INFO : seminari.irib@irib.cnr.it