Identification of ovarian cancer metastatic miRNAs
Identification of ovarian cancer metastatic miRNAs
Serous epithelial ovarian cancer (EOC) patients often succumb to aggressive metastatic disease, yet little is known about the behavior and genetics of ovarian cancer metastasis. Here, we aim to understand how omental metastases differ from primary tumors and how these differences may influence chemotherapy. We analyzed the miRNA expression profiles of primary EOC tumors and their respective omental metastases from 9 patients using miRNA Taqman qPCR arrays. We find 17 miRNAs with differential expression in omental lesions compared to primary tumors. miR-21, miR-150, and miR-146a have low expression in most primary tumors with significantly increased expression in omental lesions, with concomitant decreased expression of predicted mRNA targets based on mRNA expression. We find that miR-150 and miR-146a mediate spheroid size. Both miR-146a and miR-150 increase the number of residual surviving cells by 2–4 fold when challenged with lethal cisplatin concentrations. These observations suggest that at least two of the miRNAs, miR-146a and miR-150, up-regulated in omental lesions, stimulate survival and increase drug tolerance. Our observations suggest that cancer cells in omental tumors express key miRNAs differently than primary tumors, and that at least some of these microRNAs may be critical regulators of the emergence of drug resistant disease.
e58226
Vang, Souriya
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Wu, Hsin-Ta
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Fischer, Andrew
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Miller, Daniel H
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MacLaughlan, Shannon
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Douglass, Elijah
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Steinhoff, Margaret
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Collins, Colin
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Smith, Peter J.S.
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Brard, Laurent
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Brodsky, Alexander S
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12 March 2013
Vang, Souriya
4b061075-cb73-4b6a-ac26-9a1c7e326310
Wu, Hsin-Ta
20797795-a54d-4265-acd3-91a58493da7d
Fischer, Andrew
20b487bf-e73c-4eff-925c-cc2ade341865
Miller, Daniel H
ebca2d7d-989a-4e25-b75a-ba97839c942c
MacLaughlan, Shannon
c8096b9e-3ea3-40d0-bb91-724fff817b9b
Douglass, Elijah
c2bc854e-fc55-48c1-a0ad-a17b9f0edf25
Steinhoff, Margaret
2c4d5288-a80e-49e0-a338-5211f5aa3f4f
Collins, Colin
c8ad5faf-696f-4fa0-8363-d698a7cbc63e
Smith, Peter J.S.
003de469-9420-4f12-8f0e-8e8d76d28d6c
Brard, Laurent
0f3d972b-ff5a-4ad2-854e-f3b8216e2424
Brodsky, Alexander S
0131c984-94d2-4272-b49d-302f88cd9255
Vang, Souriya, Wu, Hsin-Ta, Fischer, Andrew, Miller, Daniel H, MacLaughlan, Shannon, Douglass, Elijah, Steinhoff, Margaret, Collins, Colin, Smith, Peter J.S., Brard, Laurent and Brodsky, Alexander S
(2013)
Identification of ovarian cancer metastatic miRNAs.
PLoS ONE, 8 (3), .
(doi:10.1371/journal.pone.0058226).
(PMID:23554878)
Abstract
Serous epithelial ovarian cancer (EOC) patients often succumb to aggressive metastatic disease, yet little is known about the behavior and genetics of ovarian cancer metastasis. Here, we aim to understand how omental metastases differ from primary tumors and how these differences may influence chemotherapy. We analyzed the miRNA expression profiles of primary EOC tumors and their respective omental metastases from 9 patients using miRNA Taqman qPCR arrays. We find 17 miRNAs with differential expression in omental lesions compared to primary tumors. miR-21, miR-150, and miR-146a have low expression in most primary tumors with significantly increased expression in omental lesions, with concomitant decreased expression of predicted mRNA targets based on mRNA expression. We find that miR-150 and miR-146a mediate spheroid size. Both miR-146a and miR-150 increase the number of residual surviving cells by 2–4 fold when challenged with lethal cisplatin concentrations. These observations suggest that at least two of the miRNAs, miR-146a and miR-150, up-regulated in omental lesions, stimulate survival and increase drug tolerance. Our observations suggest that cancer cells in omental tumors express key miRNAs differently than primary tumors, and that at least some of these microRNAs may be critical regulators of the emergence of drug resistant disease.
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Published date: 12 March 2013
Organisations:
Centre for Biological Sciences
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Local EPrints ID: 356616
URI: http://eprints.soton.ac.uk/id/eprint/356616
ISSN: 1932-6203
PURE UUID: 762ce118-3fc9-4d62-b958-1cccb69e5f3b
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Date deposited: 13 Sep 2013 13:39
Last modified: 15 Mar 2024 03:39
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Author:
Souriya Vang
Author:
Hsin-Ta Wu
Author:
Andrew Fischer
Author:
Daniel H Miller
Author:
Shannon MacLaughlan
Author:
Elijah Douglass
Author:
Margaret Steinhoff
Author:
Colin Collins
Author:
Laurent Brard
Author:
Alexander S Brodsky
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