mTOR expression by miR-99a was rescued by transfection of mTOR cDNA plasmid that lacks the 39-UTR. This findings support a model where miR-99a directly inhibits mTOR expression in breast cancer via binding to mTOR 39-UTR. mTOR is a protein kinase in the PI3K/Akt signaling pathway and mTOR protein can phosphorylate and activate its downstream effectors S6K1 and 4E-BP1 in control of protein translation and regulate cell proliferation and cell cycle. Aberrant gene expression of mTOR pathway alters cell growth and apoptosis in many cancer types such as prostate cancer, lung cancer, acute myelogenous leukemia, hepatocellular carcinoma, gastric cancer and breast cancer. In breast cancer, 44.9% of tumor tissues had increased levels of mTOR, while 71.9% of invasive breast cancer tissues expressed high level of phosphorylated S6K1 protein. Other studies reported overexpression of mTOR and its substrate in breast cancer tissue and cell lines. In our study, we found that knockdown of mTOR expression using mTOR siRNA decreased breast cancer cell viability and induced apoptosis, a similar outcome to that of tumor cells transfected with miR-99a mimics. Furthermore, the inhibition of breast cancer cell viability and the acceleration of apoptosis by miR-99a mimics were rescued by restoration of mTOR expression. The results indicated that mTOR was required for the miR-99a-dependent cell viability and apoptosis effect in breast cancer cells. Activation of S6K1 protein enhances the translation of cellular mRNAs with a 59-terminal oligopyrimidine tract and such mRNAs exclusively encode for components of the translation apparatus and control cell growth. Activation of 4E-BP1 protein results in an increase in cap-dependent mRNAs, which also promote cell growth. In contrast, inhibition of mTOR expression decreases expression of S6K1 and 4E-BP1, and subsequently leads to the reduction of mRNAs translation for negative regulators of cell cycle progression and cell proliferation, such as cyclin D1, c-Myc, Bcl-2, BclxL and eIF4B. Overexpression of 4E-BP1 or S6K1 leads to aggressive phenotypes of various cancer, such as advanced stages of disease and poor prognosis of breast cancer. In our current study, we found that the expression of phosphorylated 4E-BP1 and S6K1 was significantly reduced after inhibition of mTOR expression by miR-99a mimics in breast cell lines, concurrent with a reduction of cell viability and induction of apoptosis, while re-expression of mTOR could completely overcome the inhibitory effect of miR-99a on expression of mTOR/p-4E-BP1/p-S6K1 signal pathway genes. Thus, the current study provides a strong support of miR-99-targeted mTOR/p-4E-BP1/p-S6K1 signaling pathway in breast cancer cells. Further studies will explore whether targeting of this gene pathway could WY 14643 50892-23-4 effectively treat breast cancer. Th17 cell has been found to play important roles in both neutrophil and eosinophil mediated inflammation in asthma, but its function in AR and its response to SIT have been studied less.