Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 286, Issue 15, Pages 13714-13722Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M110.204131
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Funding
- National Basic Research Program of China 973 Program [2007CB914804, 2007CB914802, 2009CB521702]
- Natural Scientific Foundation of China [30770826, 81071623]
- Tianjin Natural Scientific Foundation [08JCZDJC20700]
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MicroRNAs play important roles in tumor metastasis. Recently, we reported that the level of miR-520b is inversely related to the metastatic potential of breast cancer cells. In this study, we investigated the role of miR-520b in breast cancer cell migration. We found that miR-520b suppressed the migration of breast cancer cells with high metastatic potential, including M DA-MB-231 and LM-MCF-7 cells, although the inhibition of miR-520b enhanced the migration of low metastatic potential MCF-7 cells. We further discovered that miR-520b directly targets the 3'-untranslated region (3'UTR) of either hepatitis B X-interacting protein (HBXIP) or interleukin-8 (IL-8), which has been reported to contribute to cell migration. Surprisingly, tissue array assays showed that 75% (38:49) and 94% (36:38) of breast cancer tissues and metastatic lymph tissues, respectively, were positive for HBXIP expression. Moreover, overexpression of HBXIP was able to promote the migration of MCF-7 cells. Interestingly, HBXIP was able to regulate IL-8 transcription by NF-kappa B, suggesting that the two target genes of miR-520b are functionally connected, In addition, we found that miR-520b could indirectly regulate IL-8 transcription by targeting HBXIP. Thus, we conclude that miR-520b is involved in regulating breast cancer cell migration by targeting HBXIP and IL-8 via a network in which HBXIP promotes migration by stimulating NF-kappa B-mediated IL-8 expression. These studies point to HBXIP as a potential therapeutic target for breast cancer.
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