期刊
MOLECULAR THERAPY-ONCOLYTICS
卷 15, 期 -, 页码 79-90出版社
CELL PRESS
DOI: 10.1016/j.omto.2019.08.009
关键词
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资金
- National Natural Science Foundation of China [81672376, 81602102]
- Medical Innovation Project of Fujian Province [2016-CX-48]
- Scientific Foundation of Fuzhou City [2015-S-143-19]
- Natural Science Foundation of Fujian Province [2016J01417]
- Fuzhou Health and Family Planning Science and Technology Project [2017-S-wt2]
- Young and Middle-Aged Talent Training Project of Fujian Provincial Health and Family Planning Commission [2018-ZQN-76, 2018-ZQN-37, 2016-1-44]
- Joint Funds for the Innovation of Science and Technology of Fujian Province [2017Y9116, 2017Y9041]
Increasing evidence has demonstrated the essential role of inflammatory micro-environment in tumorigenesis and tumor progression. Some cancer cells in tumor maintain typical stemness properties and, with the capacity of self-renewal, are thought to be crucial for the initiation and maintenance of tumors as well as their metastasis. Although both inflammatory micro-environment and stemness properties played crucial roles in tumor initiation and development, currently it is still unclear whether and how the inflammatory micro-environment promotes cancer stemness properties. Here, we show the first evidence that the inflammatory micro-environment promotes the stemness properties and metastatic potential of hepatocellular carcinoma (HCC) via the NF-kappa B/miR-497/SALL4 axis. We discover that miR-497 directly targets SALL4, negatively regulates its expression, and further inhibits the self-renewal and metastasis of HCC; more importantly, inflammatory factor TNF-alpha inhibits the expression of miR-497 via NF-kappa B-mediated negative transcriptional regulation and simultaneously upregulates the expression of SALL4 and promotes the self-renewal and metastasis phenotypes of HCC cells. Moreover, lower expression of miR-497 is significantly associated with poor prognosis in HCC patients. Taken together, our findings not only revealed a novel signaling pathway (NF-kappa B/miR-497/SALL4 axis) to connect inflammation with stemness properties, and clarified the molecular mechanisms underlying the inflammation-mediated self-renewal and metastasis phenotypes, but also provided novel molecular targets for developing new anticancer strategies.
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