CCT137690 对 MCF-7 和 MDA-MB-231 细胞系中长链非编码 RNA 表达谱的影响。
Effect of CCT137690 on long non-coding RNA expression profiles in MCF-7 and MDA-MB-231 cell lines.
机构信息
Medical Biology Department, Vocational School of Health Services, Near East University, Nicosia, TRNC.
Department of Medical Biology, Faculty of Medicine, Ege University, Bornova, Izmir, Turkey.
出版信息
Bosn J Basic Med Sci. 2020 Feb 5;20(1):56-62. doi: 10.17305/bjbms.2019.4155.
Long non-coding RNAs (lncRNAs) are involved in a range of biological processes, such as cellular differentiation, migration, apoptosis, invasion, proliferation, and transcriptional regulation. The aberrant expression of lncRNAs plays a significant role in several cancer types. Aurora kinases are increasingly expressed in various malignancies; accordingly, the inhibition of these enzymes may represent a novel approach for the treatment of various cancers. CCT137690, an Aurora kinase inhibitor, displays an anti-proliferative activity in human cancer cell lines. The aim of the present study was to investigate the anti-proliferative and cytotoxic effects of CCT137690 on estrogen receptor (ER)-positive human breast cancer cell line (MCF-7) and ER-negative human breast cancer cell line (MDA-MB-231). In addition, this study was targeted toward determining the changes induced in lncRNA expression levels following the initiation of Aurora kinase inhibitor treatment. The cytotoxic effects of CCT137690 were determined by means of the xCELLigence system. Furthermore, the anti-proliferative role of CCT137690 in breast cancer was investigated by checking the changes in lncRNA expression profiles using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The half-maximal inhibitory concentrations (IC50) of CCT137690 were determined as 4.5 μM (MCF-7) and 7.27 μM (MDA-MB-231). Several oncogenic lncRNAs (e.g., PRINS, HOXA1AS, and NCRMS) were downregulated in both ER-negative and ER-positive cell lines. On the other hand, tumor suppressor lncRNAs (e.g., DGCR5 and IGF2AS) were upregulated in the ER-positive cell line. After CCT137690 treatment, HOXA11AS and PCAT-14 lncRNAs were downregulated in the ER-positive cell lines. In addition, MER11C, SCA8, BC200, HOTAIR, PCAT-1, UCA1, SOX2OT, and HULC lncRNAs were downregulated in the ER-negative cell lines. The results of the present study indicated that Aurora kinase inhibitor CCT137690 could be a potential anti-cancer agent for breast cancer treatment.
长链非编码 RNA（lncRNA）参与多种生物学过程，如细胞分化、迁移、凋亡、侵袭、增殖和转录调控。lncRNA 的异常表达在多种癌症类型中起重要作用。Aurora 激酶在各种恶性肿瘤中表达增加；因此，抑制这些酶可能代表治疗各种癌症的新方法。Aurora 激酶抑制剂 CCT137690 在人癌细胞系中表现出抗增殖活性。本研究旨在研究 CCT137690 对雌激素受体（ER）阳性人乳腺癌细胞系（MCF-7）和 ER 阴性人乳腺癌细胞系（MDA-MB-231）的抗增殖和细胞毒性作用。此外，本研究旨在确定 Aurora 激酶抑制剂治疗开始后 lncRNA 表达水平的变化。CCT137690 的细胞毒性作用通过 xCELLigence 系统确定。此外，通过使用定量逆转录聚合酶链反应（qRT-PCR）检查 lncRNA 表达谱的变化，研究了 CCT137690 在乳腺癌中的抗增殖作用。CCT137690 的半最大抑制浓度（IC50）分别为 4.5 μM（MCF-7）和 7.27 μM（MDA-MB-231）。几种致癌 lncRNA（例如 PRINS、HOXA1AS 和 NCRMS）在 ER 阴性和 ER 阳性细胞系中均下调。另一方面，肿瘤抑制性 lncRNA（例如 DGCR5 和 IGF2AS）在 ER 阳性细胞系中上调。在 CCT137690 处理后，HOXA11AS 和 PCAT-14 lncRNA 在 ER 阳性细胞系中下调。此外，在 ER 阴性细胞系中，MER11C、SCA8、BC200、HOTAIR、PCAT-1、UCA1、SOX2OT 和 HULC lncRNA 下调。本研究结果表明，Aurora 激酶抑制剂 CCT137690 可能是治疗乳腺癌的潜在抗癌药物。
Zotero 插件