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- Title
miR-451 inhibits cell proliferation in human hepatocellular carcinoma through direct suppression of IKK-β.
- Authors
Li, He-Ping; Zeng, Xian-Cheng; Zhang, Bing; Long, Jian-Ting; Zhou, Bo; Tan, Guo-Sheng; Zeng, Wei-Xia; Chen, Wei; Yang, Jian-Yong
- Abstract
It has been demonstrated that nuclear factor-kappa B (NF-κB), which is overactivated in hepatocellular carcinoma (HCC), plays important roles in the development of HCC. Recently, a group of dysregulated micro RNAs were reported to be involved in HCC progression. Further understanding of micro RNA-mediated regulation of NF-κB pathway may provide novel therapeutic targets for HCC. In this study, we found that miR-451 expression was markedly downregulated in HCC cells and tissues compared with immortalized normal liver epithelial cells and adjacent non- cancerous tissues, respectively. Upregulation of miR-451 inhibited, while downregulation of miR-451 promoted, the tumorigenicity of HCC cells both in vitro and in vivo. These changes in the properties of HCC cells were associated with deregulation of two well-known cellular G1/S transitional regulators, cyclin D1 and c-Myc, which are downstream targets of NF-κB pathway. Furthermore, we demonstrated that miR-451 upregulation led to downregulation of cyclin D1 and c-Myc through inhibition of NF-κB pathway initiated by direct targeting of the IKBKB 3′-untranslated region. Therefore, these results suggest that miR-451 downregulation plays an important role in promoting proliferation of HCC cells and may provide the basis for the development of novel anti-HCC therapies.
- Subjects
MICRORNA; LIVER cancer; CANCER cell proliferation; NF-kappa B; GENETIC regulation; TUMOR growth; CANCER invasiveness
- Publication
Carcinogenesis, 2013, Vol 34, Issue 11, p2443
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgt206