Ovarian Cancer Drug Resistance Of Copper Ion Transporters Hctr1 Screening And Function Of Mir - 206 Related Research

Objective:To screen the hCTR1related miRNA; and confirm whether miRNA is involved in cisplatin resistance of ovarian cancer through hCTR1.Methods:miRNAs, associated with hCTR1and drug resistance, were selected firstly by searching bio-data bases and published articles. Then, miRNAs and hCTR1were confirmed in ovarian cancer cell lines and the paired cisplatin resistance cells by Real-time PCR and Western Blot. Regulatory function of target miRNA to hCTR1expression was investigated using tansfection of miRNA mimics or inhibitor. Luciferase assay was used to identify if the function of miRNA is activating through matching the3’UTR seed region. Finally, measurement of concentration of cisplatin in cells was done by ICP-MS assay.Results: miR-206was one of the most potential miRNAs of the three miRNAs screened initially, which could suppress the expression of hCTR1, and could match the specific sequence of3’UTR of hCTR1. This study indicated that the expression of miR-206was related with the low expression of hCTR1in both mRNA and protein level. Transfection of mimics and inhibitor documented that hCTR1may be involved in regulation of hCTR1expression. Moreover, miR-206could match seed region in the3’UTR of hCTR1mRNA to decrease the transcription of mRNA by luciferase assay. ICP-MS showed that miR-206also effected the accumulation of cisplatin in ovarian cancer cells.Conclusion:miR-206could down regulate the expression of hCTR1through matching the specific sequence in3’UTR. Moreover, high expression of miR-206could reduce the cisplatin influx in ovarian cancer cells. This study suggested that miR-206may be involved in cisplatin resistance through hCTR1in ovarian cancer.