期刊
CANCER LETTERS
卷 415, 期 -, 页码 20-29出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2017.11.026
关键词
Dicer; Stromal fibroblast; Reprogram; Inflammation; Ovarian cancer
类别
资金
- National Science Foundation of China [81602284, 81372801, 81572570, 81502250, 81572725, 81772787]
- 973 Program of China [2015CB553903]
- National Science-technology Supporting Plan Projects [2015BAI13B05]
Inflammation and host stromal activation contribute significantly to ovarian cancer (OC) initiation and malignant progression. However, the complex reciprocal interactions between them are largely unknown. Here, we discovered that the tumor suppressor gene Dicer was paradoxically overexpressed in ovarian tumor stroma, and induced fibroblast activation and stromal inflammation. Dicer transformed normal fibroblasts to a carcinoma-associated fibroblast (CAF)-like state, which was morphologically spread out and functionally activated to fuel tumor invasion and metastasis. Attenuation of Dicer hampered CAF characteristics, diminished stromal inflammation and the role of fibroblasts in supporting tumor growth. Moreover, Dicer drove the expression of an inflammatory signature in fibroblasts that could be used to discriminate normal and cancerous stroma and predict the survival of patients with OC. Finally, the nuclear factor is B (NF kappa B) signaling was demonstrated to be responsible for Dicer effect on fibroblast activation and stromal inflammation, through microRNA (miR)-6780b. Our study represents the first report that characterizes Dicer expression and function in the tumor stroma, and highlights its pro-metastatic role in this context. Additionally, we suggest that the Dicer-miR6780b-NF kappa B cascade is an attractive target of choice in stroma-oriented OC therapy. (C) 2017 The Authors. Published by Elsevier B.V.
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