PREreviews de Exploring G-quadruplex structure in PRCC-TFE3 fusion Oncogene: Plausible use as anti cancer therapy for translocation Renal cell carcinoma (tRCC)

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Exploring G-quadruplex structure in PRCC-TFE3 fusion Oncogene: Plausible use as anti cancer therapy for translocation Renal cell carcinoma (tRCC)

par Neha et Parimal Das

Publié: 6 juillet 2023
Serveur de preprints: bioRxiv
DOI: 10.1101/2023.07.06.547934

Résumé

The TFE3 fusion gene, byproduct of Xp11.2 translocation, is the diagnostic marker for translocation renal cell carcinoma (tRCC). Absence of any clinically recognized therapy for tRCC, pressing a need to create novel and efficient therapeutic approaches. Previous studies shown that stabilization of the G-quadruplex structure in oncogenes suppresses their expression machinery. To combat the oncogenesis caused by fusion genes, our objective is to locate and stabilize the G-quadruplex structure within the PRCC-TFE3 fusion gene. Using the Quadruplex- forming G Rich Sequences (QGRS) mapper and the Non-B DNA motif search tool (nBMST) online server, we found putative G-quadruplex forming sequences (PQS) in the PRCC-TFE3 fusion gene. Circular dichroism demonstrating a parallel G-quadruplex in the targeted sequence. Fluorescence and UV-vis spectroscopy results suggest that pyridostatin binds to this newly discovered G-quadruplex. The PCR stop assay, as well as transcriptional or translational inhibition by PQS, revealed that stable G-quadruplex formation affects biological processes. Confocal microscopy of HEK293T cells transfected with the fusion transcript confirmed G- quadruplexes formation in cell. This investigation may shed light on G-quadruplex’s functions in fusion genes and may help in the development of therapies specifically targeted against fusion oncogenes, which would enhance the capability of current tRCC therapy approach.

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PREreview Teena Bajaj et al. du club ASAPbio Cancer Biology Crowd

Rédigé par Teena Bajaj, Emma Phillips, Veronica Busa, Arpita Ghosh, Akanksha Verma, Garima Jain, Sanskriti Saxena, Pragadeeshwara Rao R, Ghada Tagorti, Rebecca A Shelley, Isaac Arddey et Ruchika Bajaj du ASAPbio Cancer Biology Crowd

This review reflects comments and contributions by Teena Bajaj, Emma Phillips, Veronica Busa, Arpita Ghosh, Akanksha, Garima Jain, Sanskriti Saxena, Pragadeeshwara Rao R, Ghada Tagorti, Rebecca A Shelley, Isaac Arddey & Ruchika Bajaj. Review synthesized by Arpita Ghosh and Garima Jain.

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