These authors contributed equally to this work.
Genome-wide screening reveals that miR-195 targets the TNF-α/NF-κB pathway by down-regulating IκB kinase alpha and TAB3 in hepatocellular carcinoma
Article first published online: 26 JUN 2013
Copyright © 2013 by the American Association for the Study of Liver Diseases
Volume 58, Issue 2, pages 654–666, August 2013
How to Cite
Ding, J., Huang, S., Wang, Y., Tian, Q., Zha, R., Shi, H., Wang, Q., Ge, C., Chen, T., Zhao, Y., Liang, L., Li, J. and He, X. (2013), Genome-wide screening reveals that miR-195 targets the TNF-α/NF-κB pathway by down-regulating IκB kinase alpha and TAB3 in hepatocellular carcinoma. Hepatology, 58: 654–666. doi: 10.1002/hep.26378
Potential conflict of interest: Nothing to report.
Supported by grants from the National Natural Science Foundation of China (91029728, 81101481, 81125016), Shanghai Rising-Star and Young Medical Talent Training Program (11QA1406100, XYQ2011048), Shanghai Municipal Education Commission, and Shanghai Municipal Health Bureau (11SG18, 20114Y159).
- Issue published online: 29 JUL 2013
- Article first published online: 26 JUN 2013
- Accepted manuscript online: 11 MAR 2013 09:50AM EST
- Manuscript Accepted: 2 MAR 2013
- Manuscript Received: 27 SEP 2012
Nuclear factor kappa B (NF-κB) is an important factor linking inflammation and tumorigenesis. In this study we experimentally demonstrated through a high-throughput luciferase reporter screen that NF-κB signaling can be directly targeted by nearly 29 microRNAs (miRNAs). Many of these miRNAs can directly target NF-κB signaling nodes by binding to their 3′ untranslated region (UTR). miR-195, a member of the miR-15 family, is frequently down-regulated in gastrointestinal cancers, especially in hepatocellular carcinoma (HCC). The expression level of miR-195 is inversely correlated with HCC tumor size. We further show that miR-195 suppresses cancer cell proliferation and migration in vitro and reduces tumorigenicity and metastasis in vivo. Additionally, miR-195 may exert its tumor suppressive function by decreasing the expression of multiple NF-κB downstream effectors by way of the direct targeting of IKKα and TAB3. Conclusion: Multiple miRNAs are involved in the NF-κB signaling pathway and miR-195 plays important inhibitory roles in cancer progression and may be a potential therapeutic target. (Hepatology 2013;58:654–666)