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CARMA3 is overexpressed in colon cancer and regulates NF-κB activity and cyclin D1 expression.

Abstract：

:CARMA3 was recently reported to be overexpressed in cancers and associated with the malignant behavior of cancer cells. However, the expression of CARMA3 and its biological roles in colon cancer have not been reported. In the present study, we analyzed the expression pattern of CARMA3 in colon cancer tissues and found that CARMA3 was overexpressed in 30.8% of colon cancer specimens. There was a significant association between CARMA3 overexpression and TNM stage (p=0.0383), lymph node metastasis (p=0.0091) and Ki67 proliferation index (p=0.0035). Furthermore, knockdown of CARMA3 expression in HT29 and HCT116 cells with high endogenous expression decreased cell proliferation and cell cycle progression while overexpression of CARMA3 in LoVo cell line promoted cell proliferation and facilitated cell cycle transition. Further analysis showed that CARMA3 knockdown downregulated and its overexpression upregulated cyclin D1 expression and phospho-Rb levels. In addition, we found that CARMA3 depletion inhibited p-IκB levels and NF-κB activity and its overexpression increased p-IκB expression and NF-κB activity. NF-κB inhibitor BAY 11-7082 reversed the role of CARMA3 on cyclin D1 upregulation. In conclusion, our study found that CARMA3 is overexpressed in colon cancers and contributes to malignant cell growth by facilitating cell cycle progression through NF-κB mediated upregulation of cyclin D1.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Miao Z,Zhao T,Wang Z,Xu Y,Song Y,Wu J,Xu H

doi

10.1016/j.bbrc.2012.07.152

subject

Has Abstract

pub_date

2012-09-07 00:00:00

pages

781-7

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(12)01466-0

journal_volume

425

pub_type

杂志文章

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