Regulation of the transcription factor NF-κB1 by microRNA-9 in human gastric adenocarcinoma

Molecular Cancer

Research

Li-Min Guo¹  Hai-Ying Wan¹  Hua Tang¹  Tao Liu¹  Min Liu¹  Xin Li¹ 

[1] Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, 300070, Tianjin, PR China;

关键词: Enhanced Green Fluorescence Protein;    MGC803 Cell;    Human Gastric Adenocarcinoma;    Enhanced Green Fluorescence Protein Fluorescence;    Gastric Cancer Cell Growth;   

DOI  :  10.1186/1476-4598-9-16

 received in 2009-07-07, accepted in 2010-01-26,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundMicroRNAs (miRNAs) are a new class of naturally occurring, small, non-coding RNAs that regulate protein-coding mRNAs by causing mRNA degradation or repressing translation. The roles of miRNAs in lineage determination and proliferation, as well as the localization of several miRNA genes at sites of translocation breakpoints or deletions, have led to speculation that miRNAs could be important factors in the development or maintenance of the neoplastic state.ResultsWe showed that miR-9 was downregulated in human gastric adenocarcinoma. Overexpression of miR-9 suppressed the growth of human gastric adenocarcinoma cell line MGC803 cell as well as xenograft tumors derived from them in SCID mice. Bioinformatics analysis indicated a putative miR-9 binding site in the 3'-untranslated region (3'UTR) of the tumor-related gene NF-κB1 mRNA. In an EGFP reporter system, overexpression of miR-9 downregulated EGFP intensity, and mutation of the miR-9 binding site abolished the effect of miR-9 on EGFP intensity. Furthermore, both the NF-κB1 mRNA and protein levels were affected by miR-9. Finally, knockdown of NF-κB1 inhibited MGC803 cell growth in a time-dependent manner, while ectopic expression of NF-κB1 could rescue MGC803 cell from growth inhibition caused by miR-9.ConclusionThese findings indicate that miR-9 targets NF-κB1 and regulates gastric cancer cell growth, suggesting that miR-9 shows tumor suppressive activity in human gastric cancer pathogenesis.

【 授权许可】

Unknown   
© Wan et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.