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