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Inflammatory Micro-environment Contributes to Stemness Properties and Metastatic Potential of HCC via the NF-κB/miR-497/SALL4 Axis.

Bixing Zhao | Yingchao Wang | Xionghong Tan | Kun Ke | Xiaoyuan Zheng | Fei Wang | Shubing Lan | Naishun Liao | Zhixiong Cai | Yingjun Shi | Youshi Zheng | Yongping Lai | Lili Wang | Qin Li | Jingfeng Liu | Aimin Huang | Xiaolong Liu
Molecular therapy oncolytics | 2019

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-κB/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-α inhibits the expression of miR-497 via NF-kB-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-κB/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.

Pubmed ID: 31650028

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