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sEV-derived circRNA in EMT progression and treatment option in Mesothelioma

Project Member(s): Cheng, Y., Zhand, S., Lee, K., Ebrahimi Warkiani, M., Zhang, L.

Funding or Partner Organisation: iCare (iCare Dust Diseases Care Grant)
iCare (iCare Dust Diseases Care Grant)

Start year: 2024

Summary: Pleural mesothelioma (PM) is a highly aggressive tumour. Early diagnosis of PM is challenging due to the lack of obvious biomarkers. Laparoscopy and biopsy with multiple immunohistology staining are considered the current gold standard for PM diagnosis. However, these procedures are invasive and mostly unaccessible with elderly patients. While the incidence of PM is growing, sensitive and non-invasive screening tools and new biomarkers for early detection are of great interest in the clinical management of PM. Tumor-generated sEVs-derived circular RNA (exo-circRNAs) can be secreted into body fluids to have an impact on non-invasive diagnosis, tumor cell apoptosis and suppression of metastasis. They might have an important role in epithelial to mesenchymal transition (EMT)-related processes, thus the knock down of exo-circRNAs would likely suppress malignant behaviour in cancer. Our preliminary study indicated that exosome circRNAs could serve as novel non-invasive biomarkers for PM. Moreover, we aim to use knock down exo-circRNAs as a novel treatment option in mesothelioma. This proposed project will employ a novel circRNA-specific quantitative droplet digital polymerase chain reaction (ddPCR) technique to detect and validate four up-regulated circRNAs in PM cell line derived sEV and patient derived pleural effusion. Furthermore, will find out the expression of EMT markers in the PM derived sEVs and the exo-circRNAs will be knocked down to supress EMT progression. We anticipate that the successful completion of the project will provide the exo-circRNA biomarker candidates in relation to their specificity and sensitivity for PM. Additionally, the modified sEVs would be a powerful treatment option for the EMT suppression in mesothelioma.

FOR Codes: Cancer cell biology, Cancer diagnosis, Cancer therapy (excl. chemotherapy and radiation therapy), Human diagnostics, Treatment of human diseases and conditions