Recent investigations have highlighted that therapeutic artificial
microRNAs could be promising candidates for
cancer therapy through the modulation of
tumor promoter or suppressor.
MEK kinase 1 (MEKK1) is expressed by
mitogen-activated
kinase kinase kinase 1 (MAP3K1), an important
kinase that links Ras activation to MAPK signaling. In the present study, we showed that synthetic MAP3K1-targeting artificial
miRNA may provide considerable beneficial effects in the prevention of
breast cancer growth and
metastasis. We showed that MEKK1 was highly expressed in human
breast cancer specimens, compared with adjacent normal tissues. Using a
miRNA-expressing lentivirus system, we delivered a artificial
miRNA (Map3k1 amiRNA) that targets MAP3K1 into 4T1
breast cancer cells and investigated the impact of MAP3K1-targeting
miRNA on the growth and invasive behavior of
breast cancer in vitro and in vivo. We found that overexpression of Map3k1 amiRNA led to impaired activities of p-ERK and p-p38. In addition, Map3k1 amiRNA induced marked proliferative impairment and invasive attenuation in
breast cancer cells. However, Map3k1 amiRNA did not have evident influence on the apoptotic response of 4T1 cells. Moreover, using in vivo nude mice model, we identified that Map3k1 amiRNA attenuated
tumor growth and lung
metastasis of
breast cancer cells. Taken together, our findings explicitly indicated that MEKK1 exerted important oncogenic property in
breast cancer development, and MAP3K1-targeting artificial
miRNA may provide promising therapeutic effects in the treatment of
breast cancer.