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

doi:10.18632/oncotarget.4346

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

College of Medicine and Public Health

Research output: Contribution to journal › Article › peer-review

71 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 language	English
Pages (from-to)	23480-23495
Number of pages	16
Journal	Oncotarget
Volume	6
Issue number	27
DOIs	https://doi.org/10.18632/oncotarget.4346
Publication status	Published - 2015

Keywords

Mesothelioma
MicroRNA
MiR-193a
Tumor suppressor

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.4346

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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

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title = "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.",

keywords = "Mesothelioma, MicroRNA, MiR-193a, Tumor suppressor",

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

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Williams, M, Kirschner, M, Cheng, YY, 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, vol. 6, no. 27, pp. 23480-23495. https://doi.org/10.18632/oncotarget.4346

TY - JOUR

T1 - miR-193a-3p is a potential tumor suppressor in malignant pleural mesothelioma

AU - Williams, Marissa

AU - Kirschner, Michaela

AU - Cheng, Yuen Yee

AU - Hanh, Jacky

AU - Weiss, Jocelyn

AU - Mugridge, N

AU - Wright, Casey

AU - Linton, Anthony

AU - Kao, Steven

AU - Edelman, James

AU - Vallely, Michael

AU - McCaughan, Brian

AU - Cooper, Wendy

AU - Klebe, Sonja

AU - Lin, Ruby

AU - Brahmbhatt, H

AU - MacDiarmid, J

AU - van Zandwijk, Nico

AU - Reid, Glen

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - Mesothelioma

KW - MicroRNA

KW - MiR-193a

KW - Tumor suppressor

UR - http://www.scopus.com/inward/record.url?scp=84943387521&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.4346

DO - 10.18632/oncotarget.4346

M3 - Article

SN - 1949-2553

VL - 6

SP - 23480

EP - 23495

JO - Oncotarget

JF - Oncotarget

IS - 27

ER -

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

Abstract

Keywords

UN SDGs

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