lncRNA GAS5-promoted apoptosis in triple-negative breast cancer by targeting miR-378a-5p/SUFU signaling
lncRNA GAS5-promoted apoptosis in triple-negative breast cancer by targeting miR-378a-5p/SUFU signaling
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DOI：
10.1002/jcb.29445
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发表时间：
2019-11-06
影响因子：
4
通讯作者：
Xu, Han
中科院分区：
文献类型：
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作者：
Zheng, Shipeng;Li, Mengquan;Xu, Han
目的长链非编码RNA（Long-chain noncoding RNAs，lncRNA）参与调节肿瘤细胞对化疗药物的敏感性，但其具体作用机制尚不清楚。本研究旨在探讨lncRNA生长停滞特异性转录本5（GAS 5）在三阴性乳腺癌（TNBC）中的作用。方法采用实时荧光定量聚合酶链反应和流式细胞术筛选与肿瘤耐药相关的lncRNA。采用双荧光素酶报告基因检测、流式细胞术和Western blot检测miRNA 378 a-5 p和SUFU是否参与lncRNA GAS 5诱导的肿瘤细胞凋亡。建立了小鼠皮下移植瘤模型，以研究lncRNA GAS 5与体内肿瘤抗性的关系。结果紫杉醇（PTX）和顺铂（CIS）处理后，GAS 5基因表达明显下调。此外，具有低表达lncRNA GAS 5的TNBC细胞在应激条件下具有较低的凋亡百分比，尤其是在无血清培养基中。更有趣的是，TNBC患者中lncRNA GAS 5的表达水平与肿瘤对PTX和CIS的耐药性相关。此外，RNA免疫沉淀实验证实lncRNA GAS 5和miR-378可以直接相互结合。此外，SUFU的miR-378 a-5 p靶点可促进lncRNA GAS 5诱导的TNBC细胞凋亡。lncRNAGAS 5过表达MDA-231 R可增强TNBC对PTX的敏感性。结论lncRNAGAS 5可通过靶向miR-378 a-5 p/SUFU信号通路诱导TNBC细胞凋亡。
Purpose Long-chain noncoding RNAs (lncRNAs) are involved in regulating the sensitivity of cancer cells to chemotherapeutic drugs, but the specific mechanism of action is not well understood. The aim of this study was to investigate the effect of lncRNA growth-stasis specific transcript 5 (GAS5) on triple-negative breast cancer (TNBC). Methods Quantitative real-time polymerase chain reaction and flow cytometry were used to screen lncRNA associated with tumor resistance. Double luciferase reporter gene assay, flow cytometry, and Western blot assay were used to determine whether miRNA 378a-5p and SUFU were involved in tumor cell apoptosis induced by lncRNA GAS5. A mouse model of subcutaneous xenografts was established to investigate the relationship between lncRNA GAS5 and tumor resistance in vivo. Results In this study, the expression of lncRNA GAS5 was significantly downregulated in cells treated with paclitaxel (PTX) or cisplatin (CIS). Furthermore, TNBC cells with low expression of lncRNA GAS5 had a lower percentage of apoptosis under stress conditions, especially in serum-free medium. More interestingly, the expression level of lncRNA GAS5 in TNBC patients was associated with tumor resistance to PTX and CIS. In addition, RNA immunoprecipitation experiments confirmed that lncRNA GAS5 and miR-378 could directly bind to each other. Moreover, the miR-378a-5p target of SUFU could promote lncRNA GAS5-induced apoptosis of TNBC cells. Finally, lncRNA GAS5 overexpressed MDA-231R could enhance the sensitivity of TNBC to PTX. Conclusion The above results confirmed that lncRNA GAS5 could induce apoptosis in TNBC cells by targeting miR-378a-5p/SUFU signaling.