长链非编码RNA-FOXF1相邻非编码RNA在乳腺癌组织的表达及其对阿霉素敏感性的影响  

Long non-coding RNA-FOXF1 adjacent non-coding RNA as a good prognostic factor in breast cancer

作　　者：张玮[1] 沈艳艳 王晓慧[1] 郭贵龙[1] Zhang Wei;Shen Yanyan;Wang Xiaohui;Guo Guilong(Department of Thyroid and Breast Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China)

机构地区：[1]温州医科大学附属第一医院甲乳外科,325000

出　　处：《中华实验外科杂志》2019年第8期1459-1461,共3页Chinese Journal of Experimental Surgery

摘　　要：目的观察长链非编码RNA (lncRNA)-FOXF1相邻非编码RNA(FENDRR)在乳腺癌癌组织和正常乳腺组织的表达,探讨FENDRR对乳腺癌患者无复发生存率(RFS)的影响,并分析其对乳腺癌阿霉素敏感性的影响.方法收集温州医科大学第一附属医院甲乳外科20例乳腺癌患者改良根治术后的新鲜正常乳腺组织和癌组织样本,采用实时定量聚合酶链反应(Real-time PCR)明确FENDRR的表达量,并采用配对t检验分析;在线KM分析网站中,分析乳腺癌中的FENDRR的表达水平对患者RFS的影响;小干扰RNA (siRNAs)下调FENDRR后,SRB法检测MCF-7对阿霉素的半数抑制浓度(IC50),并采用Real-time PCR检测耐药相关基因的表达水平.结果在乳腺癌患者癌组织的FENDRR的表达显著低于乳腺正常组织(1.00 ±0.13比2.50±0.34,t=4.528,P<0.01);FENDRR高表达的乳腺癌患者在总人群、管腔A型、管腔B型、基底型和接受系统性治疗人群中的RFS显著高于低表达人群[P<0.01、<0.01、<0.05、<0.05、<0.01,风险比(HR)=0.67(0.57 ~0.79)、0.60(0.47 ~0.78)、0.70(0.51~0.96)、0.65(0.47~0.91)、0.61(0.49~0.76)];MCF-7在FENDRR下调后,对阿霉素的敏感性显著下降(IC50=17.40 μmol/L比36.63、38.00 μmol/L);出现耐药的机制与三磷酸腺苷结合转运蛋白B1(ABCB1)和多药耐药相关蛋白1(ABCC1)的上调有关.结论 FENDRR在乳腺癌癌组织中显著低表达,其高表达提示RFS较好,FENDRR和乳腺癌药物敏感性明显相关.Objective To test FOXF1 adjacent non-coding RNA (FENDRR) expression levels in breast cancer samples, and evaluate its effects on recurrence-free survival (RFS) in breast cancer and how FENDRR modulates drug sensitivity to doxorubicin. Methods Real-time quantitative polymerase chain reaction (Real-time PCR) and pared t test were utilized to analyze FENDRR levels in normal breast tissues and cancer tissues. Online survival analysis website was used to test the effects of FENDRR on breast cancer survival. Small interfering RNAs (siRNAs) were used to knock down FENDRR and SRB was carried out to test the response to doxorubicin. We also tested the mRNA levels of adenosine triphosphate binding cassette subfamily B member 1 (ABCB1) and multidrug resistance associated protein 1 (ABCC1) after down-regulating FENDRR. Results The FENDRR levels were lower in cancer samples than those in normal breast tissues in breast caner (1.00±0.13 vs. 2.50±0.34, t=4.528, P<0.01). RFS rate of breast cancer patients with lower levels of FENDRR was lower in all patients, the subgroups of luminal A, luminal B and basal, and patients receiving systemic treatment [P<0.01,<0.01,<0.05,<0.05 and <0.01, hazard ratio (HR)=0.67 (0.57-0.79), 0.60 (0.47-0.78), 0.70 (0.51-0.96), 0.65 (0.47-0.91) and 0.61 (0.49-0.76)]. Down-regulation of FENDRR could up-regulate the expression of ABCB1 and ABCC1, conferring resistance to doxorubicin in MCF-7 cells. Conclusion FENDRR was lower in breast cancer samples, and correlated to better survival in breast cancer. By regulating MDR-related gene expression, FENDRR modulated drug sensitivity in MCF-7 cells.

关 键 词：乳腺癌 长链非编码RNA 生存 耐药 

分 类 号：R737.9[医药卫生—肿瘤]