Wednesday, September 19th, 2018


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Overexpression of miR-134 Enhanced the Sensitivity of Breast Cancer Cells to Doxorubicin by Downregulating ABCC1 Expression
Authors:  Qianqian Wang, M.D., Zhu Wang, M.M., Qi Wang, M.M., and Jie Chen, M.D.
  Objective: To detect miR-134 and ABCC1 expressions in doxorubicin-resistant breast cancer cell line and their relationship.
Study Design:
The expressions of miR-134 in doxorubicin-resistant breast cancer MCF-7/ADR cells and nonresistant MCF-7 cells were measured by qRT-PCR. ABCC1 mRNA and protein expressions were detected by qRT-PCR and western blot, respectively. The proliferation of MCF-7/ADR cells overexpressing miR-134 was detected by MTT assay after treatment with doxorubicin at IC50. Flow cytometry was used to detect the apoptosis of MCF-7/ADR cells overexpressing miR-134.
The miR-134 expression in MCF-7/ADR cells was significantly lower than that of MCF-7 cells (p<0.01). The mRNA and protein levels of ABCC1 in MCF-7/ADR cells were significantly higher (p<0.001). After overexpression of miR-134, only ABCC1 protein expression in MCF-7/ADR cells decreased significantly (p<0.001). IC50 of MCF-7/ADR cells overexpressing miR-134 was 226 ng/mL. The proliferation of MCF-7/ADR cells overexpressing miR-134 with 226 ng/mL doxorubicin was significantly weaker than that of control group at 48 hours (p<0.05). MCF-7/ADR cells overexpressing miR-134 were significantly more prone to apoptosis than those of the control group after treatment with 226 ng/mL doxorubicin (p<0.01).
Overexpression of miR-134 in MCF-7/ADR cells facilitated doxorubicin-induced proliferation inhibitory and proapoptotic effects by down regulating ABCC1 expression, thereby augmenting cell sensitivity to doxorubicin.
Keywords:  ABCC1, antagomirs, breast cancer, co-suppression, doxorubicin, microRNAs, miR-134, RNA interference
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