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本文引用的文献

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Insulin-like growth factor 1/insulin-like growth factor 1 receptor signaling protects against cell apoptosis through the PI3K/AKT pathway in glioblastoma cells.胰岛素样生长因子1/胰岛素样生长因子1受体信号通路通过PI3K/AKT途径保护胶质母细胞瘤细胞免受细胞凋亡。
Exp Ther Med. 2018 Aug;16(2):1477-1482. doi: 10.3892/etm.2018.6336. Epub 2018 Jun 21.
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New Mechanisms of Resistance to MEK Inhibitors in Melanoma Revealed by Intravital Imaging.活体成像揭示黑色素瘤对 MEK 抑制剂产生耐药性的新机制
Cancer Res. 2018 Jan 15;78(2):542-557. doi: 10.1158/0008-5472.CAN-17-1653. Epub 2017 Nov 27.
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[Low expression of lncRNA-GAS5 promotes epithelial-mesenchymal transition of breast cancer cells in vitro].[lncRNA-GAS5低表达促进乳腺癌细胞体外上皮-间质转化]
Nan Fang Yi Ke Da Xue Xue Bao. 2017 Nov 20;37(11):1427-1435. doi: 10.3969/j.issn.1673-4254.2017.11.01.
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Negative regulation of lncRNA GAS5 by miR-196a inhibits esophageal squamous cell carcinoma growth.miR-196a对lncRNA GAS5的负调控抑制食管鳞状细胞癌的生长。
Biochem Biophys Res Commun. 2018 Jan 1;495(1):1151-1157. doi: 10.1016/j.bbrc.2017.11.119. Epub 2017 Nov 21.
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Systematic review and meta-analysis of the utility of long non-coding RNA GAS5 as a diagnostic and prognostic cancer biomarker.长链非编码RNA GAS5作为癌症诊断和预后生物标志物效用的系统评价与荟萃分析
Oncotarget. 2017 Jul 6;8(39):66414-66425. doi: 10.18632/oncotarget.19040. eCollection 2017 Sep 12.
6
Could parenchymal enhancement on contrast-enhanced spectral mammography (CESM) represent a new breast cancer risk factor? Correlation with known radiology risk factors.对比增强光谱乳腺摄影(CESM)中的实质强化能否代表一种新的乳腺癌风险因素?与已知放射学风险因素的相关性。
Clin Radiol. 2017 Dec;72(12):1085.e1-1085.e9. doi: 10.1016/j.crad.2017.07.017. Epub 2017 Sep 1.
7
GAS5 knockdown reduces the chemo-sensitivity of non-small cell lung cancer (NSCLC) cell to cisplatin (DDP) through regulating miR-21/PTEN axis.GAS5 敲低通过调控 miR-21/PTEN 轴降低非小细胞肺癌(NSCLC)细胞对顺铂(DDP)的化疗敏感性。
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8
LncRNA H19 confers chemoresistance in ERα-positive breast cancer through epigenetic silencing of the pro-apoptotic gene BIK.长链非编码RNA H19通过对促凋亡基因BIK进行表观遗传沉默,赋予雌激素受体α阳性乳腺癌化学抗性。
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9
Decreased expression of long non-coding RNA GAS5 promotes cell proliferation, migration and invasion, and indicates a poor prognosis in ovarian cancer.长链非编码RNA GAS5表达降低促进卵巢癌细胞增殖、迁移和侵袭,并提示预后不良。
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10
GAS5 is downregulated in gastric cancer cells by promoter hypermethylation and regulates adriamycin sensitivity.GAS5在胃癌细胞中因启动子高甲基化而下调,并调节阿霉素敏感性。
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上调的长链非编码 RNA GAS5 可增强三阴性乳腺癌细胞的化疗敏感性和促凋亡作用。

Up-regulated lncRNA GAS5 promotes chemosensitivity and apoptosis of triple-negative breast cancer cells.

机构信息

a Departmnet of Breast and Thyroid Surgery, People's Hospital of Ganzhou City , Ganzhou , Jiangxi Province , PR. China.

b Departmnet of Pharmacy Intravenous Admixture Services, People's Hospital of Ganzhou City , Ganzhou , Jiangxi Province , PR. China.

出版信息

Cell Cycle. 2019 Aug;18(16):1965-1975. doi: 10.1080/15384101.2019.1635870. Epub 2019 Jul 7.

DOI:10.1080/15384101.2019.1635870
PMID:31282278
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6681776/
Abstract

Up to accomplishment of this study, the role of long non-coding RNAs (lncRNAs) in breast cancer has been investigated in several researches. Nevertheless, its association with the chemosensitivity of cancer was little known. Therefore, this study is focused on lncRNA GAS5 and its influence in the chemosensitivity of triple-negative breast cancer (TNBC). Expression of GAS5 in TNBC tissues and cells was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and its methylation was evaluated using methylation-specific polymerase chain reaction (MSP). Moreover, in order to define the contributory role of GAS5 in TNBC, GAS5 expression, proliferation, and apoptosis of TNBC cells were detected by a series of experiment. Finally, the effects of GAS5 were investigated by measuring tumor formation in nude mice. GAS5 was poorly expressed in TNBC tissues and cells, which could regulate the progression of TNBC. The methylation of CpG island in the promoter region of GAS5 in MDA-MB-231 and MDA-MB-468 cells was decreased, while GAS5 expression in cells was increased. Overexpressed GAS5 reduced the inhibitory concentration (IC50) value and the cell proliferation of TNBC, and promoted their apoptosis, so as to delay the progression of TNBC. Our study provides evidence that up-regulated GAS5 suppressed the progression of TNBC and promoted chemosensitivity and apoptosis of TNBC cells. Thus, GAS5 may be a potential candidate for the treatment of TNBC.

摘要

截至本研究完成,已有多项研究探讨了长链非编码 RNA(lncRNA)在乳腺癌中的作用。然而,其与癌症化疗敏感性的关联知之甚少。因此,本研究聚焦于 lncRNA GAS5 及其对三阴性乳腺癌(TNBC)化疗敏感性的影响。采用逆转录定量聚合酶链反应(RT-qPCR)检测 TNBC 组织和细胞中 GAS5 的表达,采用甲基化特异性聚合酶链反应(MSP)评估其甲基化。此外,为了明确 GAS5 在 TNBC 中的作用,通过一系列实验检测了 GAS5 在 TNBC 细胞中的表达、增殖和凋亡。最后,通过测量裸鼠肿瘤形成来研究 GAS5 的作用。GAS5 在 TNBC 组织和细胞中表达水平较低,可调节 TNBC 的进展。MDA-MB-231 和 MDA-MB-468 细胞中 GAS5 启动子区 CpG 岛的甲基化降低,而细胞中 GAS5 的表达增加。过表达 GAS5 降低了 TNBC 的半数抑制浓度(IC50)值和细胞增殖,并促进其凋亡,从而延缓 TNBC 的进展。本研究提供的证据表明,上调的 GAS5 抑制了 TNBC 的进展,提高了 TNBC 细胞的化疗敏感性和凋亡。因此,GAS5 可能是治疗 TNBC 的潜在候选药物。