Article: article from journal or magazin.
The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis.
Nature Cell Biology
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
MicroRNAs (miRNAs) are single-stranded, noncoding RNAs that are important in many biological processes. Although the oncogenic and tumour-suppressive functions of several miRNAs have been characterized, the role of miRNAs in mediating tumour metastasis was addressed only recently and still remains largely unexplored. To identify potential metastasis-promoting miRNAs, we set up a genetic screen using a non-metastatic, human breast tumour cell line that was transduced with a miRNA-expression library and subjected to a trans-well migration assay. We found that human miR-373 and miR-520c stimulated cancer cell migration and invasion in vitro and in vivo, and that certain cancer cell lines depend on endogenous miR-373 activity to migrate efficiently. Mechanistically, the migration phenotype of miR-373 and miR-520c can be explained by suppression of CD44. We found significant upregulation of miR-373 in clinical breast cancer metastasis samples that correlated inversely with CD44 expression. Taken together, our findings indicate that miRNAs are involved in tumour migration and invasion, and implicate miR-373 and miR-520c as metastasis-promoting miRNAs.
Animals, Antigens, CD44/genetics, Antigens, CD44/metabolism, Breast Neoplasms/metabolism, Breast Neoplasms/pathology, Cell Line, Tumor, Cell Migration Assays, Cell Movement/physiology, Colonic Neoplasms/metabolism, Colonic Neoplasms/pathology, Female, Humans, Lymphatic Metastasis, Male, Mice, Mice, SCID, MicroRNAs/biosynthesis, MicroRNAs/physiology, Neoplasm Invasiveness/genetics, Neoplasm Invasiveness/pathology, Neoplasm Metastasis/genetics, Neoplasm Metastasis/pathology, Neoplasm Transplantation, Prostatic Neoplasms/metabolism, Prostatic Neoplasms/pathology, Transplantation, Heterologous
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