MATERIALS AND METHODS: In this paper, we explored the expression of
miR-29b in a cohort of 67 pairs of
formalin-fixed
paraffin-embedded specimens with detailed pathological and clinical characteristics, and further analyzed the effects of
miR-29b on the malignant phenotype of HER-2-positive
breast cancer cells and the relevant mechanisms involved.
RESULTS: We found that the
miR-29b expression is negatively associated with HER-2 expression in
breast cancer tissues. Moreover, overexpression of
miR-29b induced a complex phenotype in HER-2-positive
breast cancer cells, namely an inhibition of cell proliferation, block of G1/S phase transition, induction of cell apoptosis, suppression of cell invasion in vitro, as well as inhibition on
tumor growth in vivo, indicating that
miR-29b functions as a
tumor suppressor in HER2-positive
breast cancer cells. Further bioinformatic prediction suggested that oncogene Stat3, which is an up-stream regulator of HER-2, was a target gene of
miR-29b in
breast cancer cells. We have shown that knocking down of Stat3 attenuated the malignant phenotype of
breast cancer cells similar to overexpression of
miR-29b, while restore expression of Stat3 in HER-2-positive
breast cancer cells partially abolished the suppressive effects of
miR-29b.
CONCLUSION: Collectively, our data suggest that
miR-29b could reverse the malignant phenotype of HER-2-positvie
breast cancer through, at least partially, targeting Stat3 signaling pathway.