Exploring MicroRNA and Exosome Involvement in Malignant Pleural Mesothelioma Drug Response

Johnson, Ben and Zhuang, Ling and Rath, Emma M. and Yuen, Man Lee and Cheng, Ngan Ching and Shi, Huaikai and Kao, Steven and Reid, Glen and Cheng, Yuen Yee (2022) Exploring MicroRNA and Exosome Involvement in Malignant Pleural Mesothelioma Drug Response. Cancers, 14 (19). p. 4784. ISSN 2072-6694

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Link to published document: http://doi.org/10.3390/cancers14194784

Abstract

Malignant pleural mesothelioma (MPM) is a deadly thoracic malignancy and existing treatment options are limited. Chemotherapy remains the most widely used first-line treatment regimen for patients with unresectable MPM, but is hampered by drug resistance issues. The current study demonstrated a modest enhancement of MPM cell sensitivity to chemotherapy drug treatment following microRNA (miRNA) transfection in MPM cell lines, albeit not for all tested miRNAs. This effect was more pronounced for FAK (PND-1186) small molecule inhibitor treatment; consistent with previously published data. We previously established that MPM response to survivin (YM155) small molecule inhibitor treatment is unrelated to basal survivin expression. Here, we showed that MPM response to YM155 treatment is enhanced following miRNA transfection of YM155-resistant MPM cells. We determined that YM155-resistant MPM cells secrete a higher level of exosomes in comparison to YM155-sensitive MPM cells. Despite this, an exosome inhibitor (GW4896) did not enhance MPM cell sensitivity to YM155. Additionally, our study showed no evidence of a correlation between the mRNA expression of inhibitor of apoptosis (IAP) gene family members and MPM cell sensitivity to YM155. However, two drug transporter genes, ABCA6 and ABCA10, were upregulated in the MPM cell lines and correlated with poor sensitivity to YM155. © 2022 by the authors.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 02 Mar 2023 01:25
Last Modified: 20 Mar 2023 02:27
URI: http://eprints.victorchang.edu.au/id/eprint/1306

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