Details

Autor(en) / Beteiligte

• Wan, Hai-Ying
• Guo, Li-Min
• Liu, Tao
• Liu, Min
• Li, Xin
• Tang, Hua

Titel

Regulation of the transcription factor NF-[kappa]B1 by microRNA-9 in human gastric adenocarcinoma

Ist Teil von

• Molecular cancer, 2010-01, Vol.9, p.16

Ort / Verlag

London: BioMed Central Ltd

Erscheinungsjahr

2010

Link zum Volltext

Quelle

SpringerLink Journals - AutoHoldings

Beschreibungen/Notizen

• Background MicroRNAs (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. Results We 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-[kappa]B1 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-[kappa]B1 mRNA and protein levels were affected by miR-9. Finally, knockdown of NF-[kappa]B1 inhibited MGC803 cell growth in a time-dependent manner, while ectopic expression of NF-[kappa]B1 could rescue MGC803 cell from growth inhibition caused by miR-9. Conclusion These findings indicate that miR-9 targets NF-[kappa]B1 and regulates gastric cancer cell growth, suggesting that miR-9 shows tumor suppressive activity in human gastric cancer pathogenesis.