Expression of miR-144 and lncRNA DNAJC3-AS1 in breast cancer tissues and their roles in chemotherapy resistance of breast cancer MCF-7 cells / 中国肿瘤生物治疗杂志

ABSTRACT

@#Objective: To investigate the expressions of miR-144 and lncRNA DNAJC3-AS1 in breast cancer tissues and their effects on chemo-resistance of breast cancer MCF-7 cells. Methods: A total of 196 pairs of breast cancer tissues and corresponding adjacent normal tissues collected between January, 2012 and December, 2016 in Department of Oncology, 3201 Hospital were used for this study. The relative expressions of DNAJC3-AS1, DNAJC3 and miR-144 in collected tissues were determined using qPCR, and their impact on the survival of BC patients was also analyzed. The targeted binding relationship between DNAJC3-AS1 and miR-144 was verified by Luciferase reporter gene assay. DNAJC3-AS1 over-expression plasmid and miR-144 mimics were transfected into MCF-7 cell lines respectively, and qPCR was used to verify the transfection efficiency. The effects of DNAJC3-AS1 and miR-144 overexpression on proliferation and cisplatin sensitivity of MCF-7 cells were verified by CCK-8 assay. Results: DNAJC3-AS1 and its host gene DNAJC3 were highly expressed in BC tissues (all P<0.01), and these two were positively correlated (r=0.451, P<0.01); in addition, patients with high expressions of DNAJC3-AS1 and DNAJC3 had a shorter survival period (all P<0.01). miR-144 was highly expressed in BC tissues (P<0.01) and negatively correlated with DNAJC3-AS1 (r=-0.524, P<0.01). The average over-expressionfold for DNAJC3-AS1 was 13.47 (P<0.01), while the fold for miR-144 was 20.27 (P<0.01). Bioinformatics analysis and fluorescence reporter gene assay confirmed that DNAJC3-AS1 could specifically bind to miR-144. MCF-7 cell lines over-expressing DNAJC3-AS1 and miR-14 were successfully constructed; compared with control group, cells in DNAJC3-AS1 over-expression group exhibited significantly enhanced proliferation and reduced cisplatin-sensitivity (all P<0.01), while the cells in miR-144 over-expression group showed significantly enhanced drug sensitivity (P<0.01). Conclusion: miR-144 and lncDNAJC3-AS1 were highly expressed in BC tissues, miR-144 promotes cisplatin sensitivity of BC MCF-7 cells through targeting DNAJC3-AS1.