miR-126 and miR-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis

Yun Zhang, et al. 2013. Nat Cell Biol. 15(3):284-94.

Speaker: Yi-Ying Tsai (蔡怡瑩)                                     Time: 13:00~14:00, May. 08, 2013

Commentator: Dr. Hung-Chi Cheng (鄭宏祺博士)     Place: Room 601

Abstract

About 90% of death of cancer patients is because of metastasis. It has been proved that tumour microenvironment can influence cancer progression, angiogenesis, and metastasis. Accumulated data indicate that tumor-associated stromal cells recruited by cancer cells play an important role in shaping tumour microenvironment and promoting cancer metastasis. Previous study showed that microRNAs participate in cancer progression and metastasis through several ways. Modulating tumour microenvironment is one of them. To find out the role of microRNAs for modulating of tumour microenvironment, in this study the authors screened 242 microRNAs of human breast cancer cell lines. They found that miR-126 and miR-126* were downregulated in metastatic cells and may act as potential metastasis suppressors in breast cancer. They ectopically expressed pri-miR-126 (4T1-M) in murine mammary tumour cells and used syngenic BALB/c mice as an animal model. The results showed that 4T1-M cells have significantly reduced lung metastasis ability. Furthermore, miR-126/miR-126* targeted on different sites of 3’UTR of Sdf-1α/Cxcl12 gene and independentlyinhibited the expression of stromal cell-derived factor-1 alpha (Sdf-1α), being a well known chemokine for cells recruitment. Along with the downregulation of Sdf-1α, miR-126/miR-126* suppressed mesenchymal stem cells (MSCs) and inflammatory monocytes recruitment. The expression of miR-126 gene could be changed by methylation of Egfl7 T2 promoter. Highly methylated T-2 promoter exhibited a low expression level of miR-126 in breast cancer patients. In summary, this study explains how microRNAs influenced tumour microenvironment and establishes the correlation between miR-126/miR-126* downregulation and metastasis in breast cancer patients. This may provide a new insight for cancer therapy.

References

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