A miR-335/COX-2/PTEN axis regulates the secretory phenotype of
senescent cancer-associated fibroblasts
A miR-335/COX-2/PTEN axis regulates the secretory phenotype of
senescent cancer-associated fibroblasts
Senescent cancer-associated fibroblasts (CAF) develop a senescence-associated secretory phenotype (SASP) that is believed to contribute to cancer progression. The mechanisms underlying SASP development are, however, poorly understood. Here we examined the functional role of microRNA in the development of the SASP in normal fibroblasts and CAF. We identified a microRNA, miR-335, up-regulated in the senescent normal fibroblasts and CAF and able to modulate the secretion of SASP factors and induce cancer cell motility in co-cultures, at least in part by suppressing the expression of phosphatase and tensin homologue (PTEN). Additionally, elevated levels of cyclo-oxygenase 2 (PTGS2; COX-2) and prostaglandin E2 (PGE2) secretion were observed in senescent fibroblasts, and inhibition of COX-2 by celecoxib reduced the expression of miR-335, restored PTEN expression and decreased the pro-tumourigenic effects of the SASP. Collectively these data demonstrate the existence of a novel miRNA/PTEN-regulated pathway modulating the inflammasome in senescent fibroblasts.
1608-1635
Kabir, T.D.
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Leigh, R.J.
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Tasena, H.
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Mellone, M.
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Coletta, R.D.
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Parkinson, E.K.
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Prime, S.S.
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Thomas, G.J.
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Paterson, I.C.
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Zhou, D.Z.
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McCall, J.
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Speight, P.M.
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Lambert, D.W.
50f238f8-53f6-41d3-b59e-4928cad5e0aa
August 2016
Kabir, T.D.
ad7c0018-cf8e-4956-8d86-5e17d3a7d8d3
Leigh, R.J.
a3ff1b4c-e64f-49d3-80f0-358ce0bc56e3
Tasena, H.
50d90551-d243-4871-8ea7-6be541f01dbc
Mellone, M.
b0301b32-14f8-4203-9026-b7f90885cab9
Coletta, R.D.
470c8e89-e268-4391-ba2b-2bd6396bbbd1
Parkinson, E.K.
ca386b59-0308-468e-b58d-336d850c356c
Prime, S.S.
48f6c5dd-5160-4440-bfe9-a32258f93cdb
Thomas, G.J.
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Paterson, I.C.
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Zhou, D.Z.
e7ecb69a-df32-49e6-807e-0d9505514afe
McCall, J.
183b2bfe-729c-4710-a8af-1102f48018ee
Speight, P.M.
e5e8d0a3-c9d8-4054-aa9e-c6a186c48e9f
Lambert, D.W.
50f238f8-53f6-41d3-b59e-4928cad5e0aa
Kabir, T.D., Leigh, R.J., Tasena, H., Mellone, M., Coletta, R.D., Parkinson, E.K., Prime, S.S., Thomas, G.J., Paterson, I.C., Zhou, D.Z., McCall, J., Speight, P.M. and Lambert, D.W.
(2016)
A miR-335/COX-2/PTEN axis regulates the secretory phenotype of
senescent cancer-associated fibroblasts.
Aging, 8 (8), .
(doi:10.18632/aging.100987).
(PMID:27385366)
Abstract
Senescent cancer-associated fibroblasts (CAF) develop a senescence-associated secretory phenotype (SASP) that is believed to contribute to cancer progression. The mechanisms underlying SASP development are, however, poorly understood. Here we examined the functional role of microRNA in the development of the SASP in normal fibroblasts and CAF. We identified a microRNA, miR-335, up-regulated in the senescent normal fibroblasts and CAF and able to modulate the secretion of SASP factors and induce cancer cell motility in co-cultures, at least in part by suppressing the expression of phosphatase and tensin homologue (PTEN). Additionally, elevated levels of cyclo-oxygenase 2 (PTGS2; COX-2) and prostaglandin E2 (PGE2) secretion were observed in senescent fibroblasts, and inhibition of COX-2 by celecoxib reduced the expression of miR-335, restored PTEN expression and decreased the pro-tumourigenic effects of the SASP. Collectively these data demonstrate the existence of a novel miRNA/PTEN-regulated pathway modulating the inflammasome in senescent fibroblasts.
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Kabir et al., 2016.pdf
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Accepted/In Press date: 12 June 2016
e-pub ahead of print date: 29 June 2016
Published date: August 2016
Organisations:
Cancer Sciences
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Local EPrints ID: 402808
URI: http://eprints.soton.ac.uk/id/eprint/402808
ISSN: 1945-4589
PURE UUID: 826cc015-13c0-4a73-947b-533383ebbd22
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Date deposited: 15 Nov 2016 16:24
Last modified: 15 Mar 2024 03:26
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Contributors
Author:
T.D. Kabir
Author:
R.J. Leigh
Author:
H. Tasena
Author:
M. Mellone
Author:
R.D. Coletta
Author:
E.K. Parkinson
Author:
S.S. Prime
Author:
I.C. Paterson
Author:
D.Z. Zhou
Author:
J. McCall
Author:
P.M. Speight
Author:
D.W. Lambert
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