miR-193a-3p is a potential tumor suppressor in malignant pleural mesothelioma

Marissa Williams, Michaela Kirschner, Yuen Yee Cheng, Jacky Hanh, Jocelyn Weiss, N Mugridge, Casey Wright, Anthony Linton, Steven Kao, James Edelman, Michael Vallely, Brian McCaughan, Wendy Cooper, Sonja Klebe, Ruby Lin, H Brahmbhatt, J MacDiarmid, Nico van Zandwijk, Glen Reid

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49 Citations (Scopus)

Abstract

Malignant pleural mesothelioma (MPM) is an asbestos-induced cancer with poor prognosis that displays characteristic alterations in microRNA expression. Recently it was reported that the expression of a subset of microRNAs can distinguish between MPM and adenocarcinoma of the lung. However, the functional importance of these changes has yet to be investigated. We compared expression of miR-192, miR-193a-3p and the miR-200 family in normal pleura and MPM tumor specimens and found a statistically significant reduction in the levels of miR-193a-3p (3.1-fold) and miR-192 (2.8-fold) in MPM. Transfection of MPM cells with a miR-193a-3p mimic resulted in inhibition of growth and an induction of apoptosis and necrosis in vitro. The growth inhibitory effects of miR-193a-3p were associated with a decrease in MCL1 expression and were recapitulated by RNAi-mediated MCL1 silencing. Targeted delivery of miR-193a-3p mimic using EDV minicells inhibited MPM xenograft tumour growth, and was associated with increased apoptosis. In conclusion, miR-193a-3p appears to have importance in the biology of MPM and may represent a target for therapeutic intervention.

Original languageEnglish
Pages (from-to)23480-23495
Number of pages16
JournalOncotarget
Volume6
Issue number27
DOIs
Publication statusPublished - 2015

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    Williams, M., Kirschner, M., Cheng, Y. Y., Hanh, J., Weiss, J., Mugridge, N., Wright, C., Linton, A., Kao, S., Edelman, J., Vallely, M., McCaughan, B., Cooper, W., Klebe, S., Lin, R., Brahmbhatt, H., MacDiarmid, J., van Zandwijk, N., & Reid, G. (2015). miR-193a-3p is a potential tumor suppressor in malignant pleural mesothelioma. Oncotarget, 6(27), 23480-23495. https://doi.org/10.18632/oncotarget.4346