Research published in Cell shows that let-7 increases differentiation and reduces tumorigenicity.

Researchers say that they have discovered an miRNA that pushes cancer stem cells to become more differentiated and less tumorigenic.

In the study, the investigators began by isolating breast cancer stem cells from freshly removed tumors. They then tried to generate larger quantities of tumor stem cells by growing human breast cancer cells in immunosuppressed mice dosed with a chemotherapeutic agent.

After three months of such a regimen, nearly 75% of the cells in the retrieved tumors displayed the properties of stem cells: They had the expected cell surface markers, were highly tumorigenic and metastatic in mice, were relatively drug resistant, and could be induced to differentiate into multiple kinds of breast tissue cells.

The researchers were then able to measure levels of miRNAs. They say that cancer stem cells contained low amounts of several miRNAs compared to more mature tumor cells or stem cells that had differentiated in culture.

They zeroed in on a tumor-suppressing miRNA called let-7. When the team activated let-7 in the stem cells, they lost their ability to self-renew and began to differentiate. The cells also became less able to form tumors in mice or to metastasize.

Further studies reportedly showed that let-7 did this by switching off two cancer-related genes, the oncogene Ras and HMG2A.

The research was performed by investigators at Sun-Yat-Sen University and Harvard Medical School. The study appears in the December 14 issue of Cell.

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