14q32-encoded microRNAs mediate an oligometastatic phenotype

Abhineet Uppal; Sean C. Wightman; Stephen Mallon; Go Oshima; Sean P. Pitroda; Qingbei Zhang; Xiaona Huang; Thomas E. Darga; Lei Huang; Jorge Andrade; Huiping Liu; Mark K. Ferguson; Geoffrey L. Greene; Mitchell C. Posner; Samuel Hellman; Nikolai N. Khodarev; Ralph R. Weichselbaum

doi:10.18632/oncotarget.2920

14q32-encoded microRNAs mediate an oligometastatic phenotype

Abhineet Uppal, Sean C. Wightman, Stephen Mallon, Go Oshima, Sean P. Pitroda, Qingbei Zhang, Xiaona Huang, Thomas E. Darga, Lei Huang, Jorge Andrade, Huiping Liu, Mark K. Ferguson, Geoffrey L. Greene, Mitchell C. Posner, Samuel Hellman, Nikolai N. Khodarev, Ralph R. Weichselbaum^*

^*Corresponding author for this work

Pharmacology

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

101 Scopus citations

Abstract

Oligometastasis is a clinically distinct subset of metastasis characterized by a limited number of metastases potentially curable with localized therapies. We analyzed pathways targeted by microRNAs over-expressed in clinical oligometastasis samples and identified suppression of cellular adhesion, invasion, and motility pathways in association with the oligometastatic phenotype. We identified miR-127-5p, miR-544a, and miR-655-3p encoded in the 14q32 microRNA cluster as co-regulators of multiple metastatic pathways through repression of shared target genes. These microRNAs suppressed cellular adhesion and invasion and inhibited metastasis development in an animal model of breast cancer lung colonization. Target genes, including TGFBR2 and ROCK2, were key mediators of these effects. Understanding the role of microRNAs expressed in oligometastases may lead to improved identification of and interventions for patients with curable metastatic disease, as well as an improved understanding of the molecular basis of this unique clinical entity.

Original language	English (US)
Pages (from-to)	3540-3552
Number of pages	13
Journal	Oncotarget
Volume	6
Issue number	6
DOIs	https://doi.org/10.18632/oncotarget.2920
State	Published - 2015

Funding

Keywords

Gene expression
Gene regulation
Metastasis
MicroRNA
Oligometastasis

ASJC Scopus subject areas

Oncology

UN SDGs

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

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10.18632/oncotarget.2920

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Uppal, A., Wightman, S. C., Mallon, S., Oshima, G., Pitroda, S. P., Zhang, Q., Huang, X., Darga, T. E., Huang, L., Andrade, J., Liu, H., Ferguson, M. K., Greene, G. L., Posner, M. C., Hellman, S., Khodarev, N. N., & Weichselbaum, R. R. (2015). 14q32-encoded microRNAs mediate an oligometastatic phenotype. Oncotarget, 6(6), 3540-3552. https://doi.org/10.18632/oncotarget.2920

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abstract = "Oligometastasis is a clinically distinct subset of metastasis characterized by a limited number of metastases potentially curable with localized therapies. We analyzed pathways targeted by microRNAs over-expressed in clinical oligometastasis samples and identified suppression of cellular adhesion, invasion, and motility pathways in association with the oligometastatic phenotype. We identified miR-127-5p, miR-544a, and miR-655-3p encoded in the 14q32 microRNA cluster as co-regulators of multiple metastatic pathways through repression of shared target genes. These microRNAs suppressed cellular adhesion and invasion and inhibited metastasis development in an animal model of breast cancer lung colonization. Target genes, including TGFBR2 and ROCK2, were key mediators of these effects. Understanding the role of microRNAs expressed in oligometastases may lead to improved identification of and interventions for patients with curable metastatic disease, as well as an improved understanding of the molecular basis of this unique clinical entity.",

keywords = "Gene expression, Gene regulation, Metastasis, MicroRNA, Oligometastasis",

author = "Abhineet Uppal and Wightman, {Sean C.} and Stephen Mallon and Go Oshima and Pitroda, {Sean P.} and Qingbei Zhang and Xiaona Huang and Darga, {Thomas E.} and Lei Huang and Jorge Andrade and Huiping Liu and Ferguson, {Mark K.} and Greene, {Geoffrey L.} and Posner, {Mitchell C.} and Samuel Hellman and Khodarev, {Nikolai N.} and Weichselbaum, {Ralph R.}",

year = "2015",

doi = "10.18632/oncotarget.2920",

language = "English (US)",

volume = "6",

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AU - Uppal, Abhineet

AU - Wightman, Sean C.

AU - Mallon, Stephen

AU - Oshima, Go

AU - Pitroda, Sean P.

AU - Zhang, Qingbei

AU - Huang, Xiaona

AU - Darga, Thomas E.

AU - Huang, Lei

AU - Andrade, Jorge

AU - Liu, Huiping

AU - Ferguson, Mark K.

AU - Greene, Geoffrey L.

AU - Posner, Mitchell C.

AU - Hellman, Samuel

AU - Khodarev, Nikolai N.

AU - Weichselbaum, Ralph R.

PY - 2015

Y1 - 2015

N2 - Oligometastasis is a clinically distinct subset of metastasis characterized by a limited number of metastases potentially curable with localized therapies. We analyzed pathways targeted by microRNAs over-expressed in clinical oligometastasis samples and identified suppression of cellular adhesion, invasion, and motility pathways in association with the oligometastatic phenotype. We identified miR-127-5p, miR-544a, and miR-655-3p encoded in the 14q32 microRNA cluster as co-regulators of multiple metastatic pathways through repression of shared target genes. These microRNAs suppressed cellular adhesion and invasion and inhibited metastasis development in an animal model of breast cancer lung colonization. Target genes, including TGFBR2 and ROCK2, were key mediators of these effects. Understanding the role of microRNAs expressed in oligometastases may lead to improved identification of and interventions for patients with curable metastatic disease, as well as an improved understanding of the molecular basis of this unique clinical entity.

AB - Oligometastasis is a clinically distinct subset of metastasis characterized by a limited number of metastases potentially curable with localized therapies. We analyzed pathways targeted by microRNAs over-expressed in clinical oligometastasis samples and identified suppression of cellular adhesion, invasion, and motility pathways in association with the oligometastatic phenotype. We identified miR-127-5p, miR-544a, and miR-655-3p encoded in the 14q32 microRNA cluster as co-regulators of multiple metastatic pathways through repression of shared target genes. These microRNAs suppressed cellular adhesion and invasion and inhibited metastasis development in an animal model of breast cancer lung colonization. Target genes, including TGFBR2 and ROCK2, were key mediators of these effects. Understanding the role of microRNAs expressed in oligometastases may lead to improved identification of and interventions for patients with curable metastatic disease, as well as an improved understanding of the molecular basis of this unique clinical entity.

KW - Gene expression

KW - Gene regulation

KW - Metastasis

KW - MicroRNA

KW - Oligometastasis

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14q32-encoded microRNAs mediate an oligometastatic phenotype

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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