MiR-18a upregulation enhances autophagy in triple negative cancer cells via inhibiting mTOR signaling pathway.


OBJECTIVE We investigated the involvement of miR-18a upregulation in autophagy regulation and paclitaxel (PTX) resistance in triple negative breast cancer (TNBC) cells. MATERIALS AND METHODS PTX resistant MDA-MMB-231/PTX cells were generated using an intermittent, stepwise method. MiR-18a expression was assessed using qRT-PCR. The level of autophagy was assessed by Western blot analysis of LC3B expression and observation of LC3-GFP puncta formation under a fluorescence microscope. The effect of miR-18a mediated autophagy on PTX sensitivity was assessed by measuring IC50 and PTX induced cell apoptosis. RESULTS MDA-MB-231/PTX cells had both higher miR-18a expression and basal autophagy than MDA-MB-231 cells. Enforced miR-18a overexpression directly led to increased autophagy in MDA-MB-231 cells, the effect of which was similar to that of rapamycin, a mTOR signaling inhibitor. Following Western blot analysis showed that miR-18a overexpression decreased the expression of p-mTOR and p-p70S6. Therefore, we infer that miR-18a increases autophagy level in MDA-MB-231 cells via inhibiting mTOR signaling pathway. Both drug sensitivity assay and flow cytometry analysis confirmed that the effect of miR-18a on increasing IC50 and decreasing PTX induced apoptosis in MDA-MB-231 cells could largely be abrogated by treatment with bafilomycin A1 (Baf. A1). CONCLUSIONS MiR-18a upregulation results in enhanced autophagy via inhibiting mTOR signaling pathway in TNBC cells, which is a mechanism contributing to paclitaxel resistance.

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@article{Fan2016MiR18aUE, title={MiR-18a upregulation enhances autophagy in triple negative cancer cells via inhibiting mTOR signaling pathway.}, author={Y Y Fan and Y-Z Dai and X X Wang and Y D Ren and J L Han and H Zhang}, journal={European review for medical and pharmacological sciences}, year={2016}, volume={20 11}, pages={2194-200} }