"Endogenous human microRNAs that suppress breast cancer metastasis"
"The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis"

MicroRNAs (miRNAs) are small, noncoding RNAs that act post-transcriptionally to regulate the expression of protein-encoding genes. Emerging evidence suggests that several miRNA may be involved in human carcinogenesis and tumour-suppression. Until now, however, it had not been demonstrated that some miRNAs mediate tumour metastasis. Since miRNAs can effectively regulate the activity of multiple cancer-related genes and pathways, they are prime candidates for coordinating the intricate events that lead to the spread of cancer, which is known as metastasis. Two studies led by cancer investigators have recently identified mechanisms by which cancer cells gain the ability to metastasize.One study, published in the January 10 issue of Nature, found that the microRNAs miR-126 and miR-335 have an important role in breast cancer tumourigenesis and metastasis. When normal levels of these microRNAs are restored in the cultured human breast cancer cells, it greatly reduced the cells' ability to spread to the lungs or bones of mice. Massagu? and his colleagues found a particularly strong association between loss of miR-335 and cancer relapse, so they next elucidated that a set of six genes whose activity greatly increased with loss of miR-335 in metastatic cells. Among them, SOX4 and TNC were known to regulate cell migration, which is critical for cancer invasion of other tissues.

The second study, published online January 13 by Nature cell biology, suggests a role for microRNAs (miRNAs) in breast cancer metastasis. The investigators have identified two miRNAs that promote tumors' deadly spread, or metastasis. By a forward genetic screen using a miRNA-expression library, miR-373 and miR-520c were found in the migratory cells. Previous studies demonstrated that CD44 is a metastasis suppressor gene for some cancers.In this study, Dr. Huang demonstrated that these miRNAs promote cell metastasis by limiting the expression of CD44 in a human breast tumour cell line. An additional study of 72 human primary breast tumors found that expression of miR-126 and miR-335 is lost in the majority of primary breast tumours from patients who relapse, and the loss of expression of either miRNA is associated with poor distal metastasis-free survival.These studies represent that a specific group of miRNA molecules are responsible for controlling genes that cause cancer metastasis. Therefore, suppression of cell migration by anti-miRNA oligonucleotide may offer a promising therapeutic approach against metastasis. (Commentary : Dr.Naoko Abe, M.D.)

"Endogenous human microRNAs that suppress breast cancer metastasis"
Sohail F.Tavasoie, et al.
Nature vol451 10 January 2008 147-154

"The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis"
Qihong Huang, et al.
Nature Cell Biology advance online publication 13 January 2008 1-9

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