MicroRNA-708 as a Therapeutic Agent against Metastatic Breast Cancer

Cancer metastases result in more than 90% of cancer related deaths. Many breast cancer patients have the worst outcome due to its high rate of recurrence and metastatic spread. However, there are no approved targeted therapies for breast cancer patients with metastasis.

Cornell researchers have identified that miR-708 is suppressed in human metastatic breast cancer cells and breast cancer mouse models. Consistently with this observation, miR-708 expression level is also significantly reduced in lymph node and distal metastases in breast cancer patients. Expression of miR-708 suppresses tumor cell migration and inhibition of miR-708 stimulates tumor cell migration in vitro. Expression of miR708 in vivo inhibits lung metastases in animals.

Mechanistically, the researchers demonstrate that miR-708 inhibits the expression of the endoplasmic reticulum protein neuronatin (NNAT), which regulates intracellular calcium (Ca2+) level. The decreased intracellular Ca2+ level results in decreased cell migration and impaired metastasis. The group also demonstrates that the polycomb group complex PRC2 is involved in the suppression of miR-708 in metastatic cells.

Potential Applications

Synthetic miR-780 as novel therapeutic for metastatic breast cancer, including triple-negative breast cancer.

Advantages

Potentially the first agent to specifically treat breast cancer metastasis
Epigenetic drugs which inhibit a member of the polycomb group, may help to restore miR-708