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

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.

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@inproceedings{Williams2015miR193a3pIA, title={miR-193a-3p is a potential tumor suppressor in malignant pleural mesothelioma}, author={Marissa E Williams and Michaela B. Kirschner and Yuen Yee Cheng and Jacky Hanh and Jocelyn C Weiss and Nancy B. Mugridge and Casey M. Wright and Anthony Linton and Steven Chuan-Hao Kao and J. James B. Edelman and Michael Patrick Vallely and Brian C. McCaughan and Wendy A Cooper and Sonja Klebe and Ruby C Y Lin and Himanshu N. Brahmbhatt and J A Macdiarmid and Nico van Zandwijk and Glen Reid}, booktitle={Oncotarget}, year={2015} }