miR-451 inhibits cell proliferation in human hepatocellular carcinoma through direct suppression of IKK-β.

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.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Li HP,Zeng XC,Zhang B,Long JT,Zhou B,Tan GS,Zeng WX,Chen W,Yang JY

doi

10.1093/carcin/bgt206

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

2443-51

issue

11

eissn

0143-3334

issn

1460-2180

pii

bgt206

journal_volume

34

pub_type

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