目的：探讨miR-144及长链非编码RNA(long non-coding RNA, lncRNA）DNAJC3-AS1在乳腺癌（breat cancer, BC）组 织中的表达及其对BC MCF-7细胞化疗耐药的影响。方法：选取2012年1月至2016年12月于三二〇一医院肿瘤内科收治的 196例BC患者的肿瘤组织及其配对癌旁组织，采用qPCR法检测DNAJC3-AS1、DNAJC3及miR-144在BC组织中的相对表达量， 分析其对患者生存期的影响；荧光素酶报告基因实验验证DNAJC3-AS1与miR-144的靶向结合关系； 将DNAJC3-AS1过表达质 粒及miR-144 mimics转染MCF-7细胞，采用qPCR验证转染效果。CCK-8实验检测过表达DNAJC3-AS1及过表达miR-144对 MCF-7细胞增殖及顺铂敏感性的影响。结果：DNAJC3-AS1及其宿主基因DNAJC3在BC组织中均呈高表达（均P<0.01），且两 者表达水平呈正相关（r=0.451， P<0.01），并且高表达DNAJC3-AS1和DNAJC3的患者生存期较短（均P<0.01）；miR-144在BC组 织中呈低表达（P<0.01），且与DNAJC3-AS1呈负相关（r=–0.524， P<0.01)。转染后细胞中DNAJC3-AS1过表达平均倍数为13.47 倍（P<0.01），miR-144过表达平均倍数为20.27倍（P<0.01）；生物信息学分析和荧光素酶报告实验证实DNAJC3-AS1能够与miR-144 靶向结合。成功构建过表达DNAJC3-AS1和miR-14的MCF-7细胞，与对照组相比，DNAJC3-AS1过表达组细胞增殖能力显著增 强（P<0.01）、对顺铂的敏感性显著降低 （P<0.01），而 miR-144 过表达组细胞对顺铂的敏感性显著增加 （P<0.01）。结论：miR-144和 lncRNADNAJC3-AS1在BC组织中均高表达，miR-144可通过靶向DNAJC3-AS1从而提高BC MCF-7细胞对顺铂的敏感性。

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-expression fold 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.

广东省医学科学技术研究基金资助项目（No.A2019255）