Abstract
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.
Highlights
Estrogen receptor (ER) is a nuclear hormone receptor that is involved in the development of breast cancer [1]
MCF-7 and MDA-MB-231 cells were treated with CCT137690 for 48 h to analyze the cytotoxic effects
Untreated MCF-7 and MDA-MB-231 cells were used as the control groups
Summary
Estrogen receptor (ER) is a nuclear hormone receptor that is involved in the development of breast cancer [1]. Based on the presence of ER, breast cancer can be classified into two groups of ER-negative and ER-positive. According to a large body of evidence, approximately 80% of breast cancers are ER-positive [2]. Aurora kinases entail three isoforms of A, B, and C. Aurora kinases are the most important serine/ threonine protein kinases that regulate the function of centrosomes, spindle, and kinetochores for appropriate mitotic progression.
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