A miR-335/COX-2/PTEN axis regulates the secretory phenotype of senescent cancer-associated fibroblasts

被引：68

作者：

Kabir, Tasnuva D. ^{[1
,2
]}

Leigh, Ross J. ^{[1
]}

Tasena, Hataitip ^{[1
]}

Mellone, Massimiliano ^{[3
]}

Coletta, Ricardo D. ^{[4
]}

Parkinson, Eric K. ^{[5
]}

Prime, Stephen S. ^{[5
]}

Thomas, Gareth J. ^{[3
]}

Paterson, Ian C. ^{[6
,7
]}

Zhou, Donghui ^{[8
]}

McCall, John ^{[2
]}

Speight, Paul M. ^{[1
]}

Lambert, Daniel W. ^{[1
]}

机构：

[1] Univ Sheffield, Sch Clin Dent, Integrated Biosci, Sheffield S10 2TA, S Yorkshire, England

[2] Univ Otago, Dunedin Hosp, Dunedin Med Sch, Dept Surg Sci, Dunedin 9016, New Zealand

[3] Univ Southampton, Fac Med, Canc Sci Unit, Somers Bldg, Southampton SO16 6YD, Hants, England

[4] Univ Estadual Campinas, Sch Dent, Dept Oral Diag, Piracicaba, SP, Brazil

[5] Queen Mary Univ London, Barts & London Sch Med & Dent, Inst Dent, Ctr Clin & Diagnost Oral Sci, London E1 2AD, England

[6] Univ Malaya, Fac Dent, Dept Oral & Craniofacial Sci, Malaya, Malaysia

[7] Univ Malaya, Fac Dent, Oral Canc Res & Coordinating Ctr, Malaya, Malaysia

[8] Univ Otago, Sch Med Sci, Dept Biochem, Dunedin 9054, New Zealand

来源：

AGING-US | 2016年 / 8卷 / 08期

关键词：

miR-335; PTEN; fibroblast; CAF; SASP; COX-2; SQUAMOUS-CELL CARCINOMA; TUMOR MICROENVIRONMENT; STROMAL FIBROBLASTS; OXIDATIVE STRESS; DOWN-REGULATION; PTEN ACTIVITY; ACTIVATION; MIR-335; DIFFERENTIATION; CHEMOTHERAPY;

D O I：

10.18632/aging.100987

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1608 / 1635

页数：28

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