miR-222 induces Adriamycin resistance in breast cancer through PTEN/Akt/p27 kip1 pathway

AbstractThe high resistant rate of Adriamycin (Adr) is associated with a poor prognosis of breast cancer in women worldwide. SincemiR-222 might contribute to chemoresistance in many cancer types, in this study, we aimed to investigate its efficacy in breast cancer throughPTEN/Akt/p27kip1 pathway. Firstly, in vivo, we verified thatmiR-222 was upregulated in chemoresistant tissues after surgery compared with the paired preneoadjuvant samples of 21 breast cancer patients. Then, human breast cancer Adr-resistant cell line (MCF-7/Adr) was constructed to validate the pathway from the parental sensitive cell line (MCF-7/S). MCF-7/Adr and MCF-7/S were transfected with miR-222 mimics, miR-222 inhibitors, or their negative controls, respectively. The results showed that inhibition ofmiR-222 in MCF-7/Adr significantly increased the expressions ofPTEN andp27kip1 and decreasedphospho-Akt (p-Akt) both in mRNA and protein levels (p <  0.05) by using quantitative real-time PCR (qRT-PCR) and western blot. MTT and flow cytometry suggested that lower expressedmiR-222 enhanced apoptosis and decreased the IC50 of MCF-7/Adr cells. Additionally, immunofluorescence demonstrated that the subcellular location ofp27kip1 was dislocated resulting from the alteration ofmiR-222. Conversely, in MCF-7/S transfected with miR-222 mimics, upregulation ofmiR-222 is associated with decreasingPTEN andp27kip1 and increasingAkt accompanied by less apoptosis and higher IC50. Importantly, Adr resistance induced b...
Source: Tumor Biology - Category: Cancer & Oncology Source Type: research