LncRNA LOC100505501在柴胡皂苷D逆转MCF-7/ADR细胞耐药中的作用  

Effect of LOC100505501 on saikosaponin D-mediated reversal of breast cancer multidrug resistance in MCF-7/ADR cells

作　　者：黄瑞红[1] 阳巧凤[1] 黄瑞玉[2] 周升铭 HUANG Rui-hong;YANG Qiao-feng;HUANG Rui-yu;ZHOU Sheng-ming(Department of Pharmacy Maternal and Child Health Care Hospital of Guangdong,Guangzhou 510010;Clinical Laboratory of Maternal and Child Health Care Hospital of Guangdong,Guangzhou 510010)

机构地区：[1]广东省妇幼保健院药学部,广州510010 [2]广东省妇幼保健院检验科,广州510010

出　　处：《中南药学》2018年第12期1720-1724,共5页Central South Pharmacy

基　　金：2017年广东省中医药局面上科研项目(编号:20172016)

摘　　要：目的通过基因表达数据库和癌症基因组图谱数据库寻找与柴胡皂苷D(SSd)介导的乳腺癌多药耐药(MDR)逆转相关的长链非编码RNA(lncRNA),并分析其效应机制。方法筛选基因表达数据库MCF-7、MCF-7/ADR差异表达谱(GSE76540)和SSd处理MCF-7前后差异表达谱(GSE85871)的交集lncRNA,分析癌症基因组图谱数据与乳腺癌预后的关联。针对显著关联的lncRNA,采用CCK8法、流式细胞术和荧光定量PCR法观察其对SSd介导的MCF-7/ADR细胞表型效应的影响及机制。结果仅发现1个交集lncRNALOC100505501,其在MCF-7/ADR中高表达,SSd处理可导致其表达下调。癌症基因组图谱数据显示LOC100505501高表达会导致患者预后差(P=0.023)。该lncRNA过表达可弱化SSd对MCF-7/ADR细胞增殖的抑制,降低SSd的抗凋亡效果,导致耐药逆转倍数降低(1.95至1.36)。此外,该lncRNA与P-gp蛋白的表达呈显著正相关,可上调MCF-7/ADR细胞P-gp蛋白的表达。结论 LOC100505501可通过上调P-gp蛋白的表达而阻滞SSd介导的细胞增殖抑制、凋亡促进和耐药逆转效应,可作为乳腺癌MDR潜在的药物靶点。Objective To determine the effect of long non-coding RNA (hacRNA)on the reversal of multidrug resistance in breast cancer induced by saikosaponin D (SSd)based on the GEO datasets and TCGA database,and to analyze the biological mechanism of the lncRNA.Methods We searched two GEO datasets,namely expression data from MCF-7and MCF-7/ADR cells (GSE76540)and gene expression profiles of MCF7cells treated with traditional Chinese medicine components (GSE85871).We identified overlapped differentially expressed lncRNA between the two groups,and analyzed the effects of those lncRNAs on breast cancer survival with the TCGA data.Then we conducted CCK8assay,flow cytometry and real-time quantitative PCR to assess the effect as well as mechanism of one promising lncRNA on SSd-mediated reversal of breast cancer multidrug resistance in MCF-7/ ADR cells.Results We only identified one overlapped lncRNA that was LOC 100505501.The lncRNA was highly expressed in MCF-7/ADR than in MCF-7,and SSd decreases its expression in MCF-7.The TCGA data further showed that the high level of LOC 100505501deteriorated the survival of breast cancer patients in comparison to that of low level (P =0.023).Overexpression of LOC100505501antagonized the inhibition role of SSd on MCF- 7/ADK cells including reduced tumor cellular proliferation inhibition and apoptosis rate,which ultimately resulted in a decline in the reversal index (from 1.95to 1.36).Moreover,the lncRNA level was positively correlated with P-gpexpression,and its overexpression upregulated P-gp.Conclusion LOC100505501can antagonize the inhibition of SSd on MCF-7/ADR cells,which may be a possible drug target for breast cancer treatment.

关 键 词：长链非编码RNA 乳腺癌 多药耐药 柴胡皂苷D LOC100505501 

分 类 号：R737.9[医药卫生—肿瘤]