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

Marissa Williams; Michaela B. Kirschner; Yuen Yee Cheng; Jacky Hanh; Jocelyn Weiss; Nancy Mugridge; Casey M. Wright; Anthony Linton; Steven C. Kao; J. James B. Edelman; Michael P. Vallely; Brian C. McCaughan; Wendy Cooper; Sonja Klebe; Ruby C. Y. Lin; Himanshu Brahmbhatt; Jennifer 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 B. Kirschner, Yuen Yee Cheng, Jacky Hanh, Jocelyn Weiss, Nancy Mugridge, Casey M. Wright, Anthony Linton, Steven C. Kao, J. James B. Edelman, Michael P. Vallely, Brian C. McCaughan, Wendy Cooper, Sonja Klebe, Ruby C. Y. Lin, Himanshu Brahmbhatt, Jennifer MacDiarmid, Nico van Zandwijk, Glen Reid

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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

Bibliographical note

Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

tumor suppressor
mesothelioma
microRNA
miR-193a

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10.18632/oncotarget.4346

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Williams, M., Kirschner, M. B., Cheng, Y. Y., Hanh, J., Weiss, J., Mugridge, N., Wright, C. M., Linton, A., Kao, S. C., Edelman, J. J. B., Vallely, M. P., McCaughan, B. C., Cooper, W., Klebe, S., Lin, R. C. Y., 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

@article{49b2dab9ef284f518a35cc6302c404cd,

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 = "tumor suppressor, mesothelioma, microRNA, miR-193a",

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

note = "Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2015",

doi = "10.18632/oncotarget.4346",

language = "English",

volume = "6",

pages = "23480--23495",

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Williams, M, Kirschner, MB, Cheng, YY, Hanh, J, Weiss, J, Mugridge, N, Wright, CM, Linton, A, Kao, SC, Edelman, JJB, Vallely, MP, McCaughan, BC, Cooper, W, Klebe, S, Lin, RCY, 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 B.

AU - Cheng, Yuen Yee

AU - Hanh, Jacky

AU - Weiss, Jocelyn

AU - Mugridge, Nancy

AU - Wright, Casey M.

AU - Linton, Anthony

AU - Kao, Steven C.

AU - Edelman, J. James B.

AU - Vallely, Michael P.

AU - McCaughan, Brian C.

AU - Cooper, Wendy

AU - Klebe, Sonja

AU - Lin, Ruby C. Y.

AU - Brahmbhatt, Himanshu

AU - MacDiarmid, Jennifer

AU - van Zandwijk, Nico

AU - Reid, Glen

N1 - Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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 - tumor suppressor

KW - mesothelioma

KW - microRNA

KW - miR-193a

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

U2 - 10.18632/oncotarget.4346

DO - 10.18632/oncotarget.4346

M3 - Article

C2 - 26125439

VL - 6

SP - 23480

EP - 23495

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 27

ER -

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

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