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头颈部鳞状细胞癌(HNSCC)细胞系经照射和化疗暴露后的长链非编码RNA(lncRNA)表达

lncRNA Expression after Irradiation and Chemoexposure of HNSCC Cell Lines.

作者信息

Guglas Kacper, Kolenda Tomasz, Teresiak Anna, Kopczyńska Magda, Łasińska Izabela, Mackiewicz Jacek, Mackiewicz Andrzej, Lamperska Katarzyna

机构信息

Laboratory of Cancer Genetics, Greater Poland Cancer Centre, 61-866 Poznan, Poland.

Postgraduate School of Molecular Medicine, Medical University of Warsaw, 02-091 Warszawa, Poland.

出版信息

Noncoding RNA. 2018 Nov 14;4(4):33. doi: 10.3390/ncrna4040033.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause of cancer mortality in the world. To improve the quality of diagnostics and patients' treatment, new and effective biomarkers are needed. Recent studies have shown that the expression level of different types of long non-coding RNAs (lncRNAs) is dysregulated in HNSCC and correlates with many biological processes. In this study, the response of lncRNAs in HNSCC cell lines after exposure to irradiation and cytotoxic drugs was examined. The SCC-040, SCC-25, FaDu, and Cal27 cell lines were treated with different radiation doses as well as exposed to cisplatin and doxorubicin. The expression changes of lncRNAs after exposure to these agents were checked by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Target prediction was performed using available online tools and classified into specific biological processes and cellular pathways. The results indicated that the irradiation, as well as chemoexposure, causes changes in lncRNA expression and the effect depends on the cell line, type of agents as well as their dose. After irradiation using the dose of 5 Gy significant dysregulation of 4 lncRNAs, 10 Gy-5 lncRNAs, and 20 Gy-3 lncRNAs, respectively, were observed in all cell lines. Only lncRNAs Zfhx2as was down-regulated in all cell lines independently of the dose used. After cisplatin exposure, 14 lncRNAs showed lower and only two higher expressions. Doxorubicin resulted in lower expressions of eight and increased four of lncRNAs. Common effects of cytotoxic drugs were observed in the case of antiPEG11, BACE1AS, PCGEM1, and ST7OT. Analysis of the predicted targets for dysregulated lncRNAs indicated that they are involved in important biological processes, regulating cellular pathways connected with direct response to irradiation or chemoexposure, cellular phenotype, cancer initiating cells, and angiogenesis. Both irradiation and chemoexposure caused specific changes in lncRNAs expression. However, the common effect is potentially important for cellular response to the stress and survival. Further study will show if lncRNAs are useful tools in patients' treatment monitoring.

摘要

头颈部鳞状细胞癌(HNSCC)是全球第六大常见癌症死亡原因。为了提高诊断质量和患者治疗效果,需要新的有效生物标志物。最近的研究表明,不同类型的长链非编码RNA(lncRNA)在HNSCC中的表达水平失调,并与许多生物学过程相关。在本研究中,检测了HNSCC细胞系在暴露于辐射和细胞毒性药物后lncRNA的反应。SCC - 040、SCC - 25、FaDu和Cal27细胞系接受了不同的辐射剂量,并暴露于顺铂和阿霉素中。通过定量逆转录 - 聚合酶链反应(qRT - PCR)检测暴露于这些药物后lncRNA的表达变化。使用可用的在线工具进行靶标预测,并将其分类为特定的生物学过程和细胞途径。结果表明,辐射以及化学药物暴露会导致lncRNA表达发生变化,其影响取决于细胞系、药物类型及其剂量。在所有细胞系中,使用5 Gy剂量辐射后,分别观察到4种lncRNA显著失调,10 Gy剂量下5种lncRNA失调,20 Gy剂量下3种lncRNA失调。仅lncRNA Zfhx2as在所有细胞系中均下调,与所用剂量无关。顺铂暴露后,14种lncRNA表达降低,仅2种lncRNA表达升高。阿霉素导致8种lncRNA表达降低,4种lncRNA表达升高。在antiPEG11、BACE1AS、PCGEM1和ST7OT的情况下观察到细胞毒性药物的共同作用。对失调lncRNA预测靶标的分析表明,它们参与重要的生物学过程,调节与辐射或化学药物暴露的直接反应、细胞表型、癌症起始细胞和血管生成相关的细胞途径。辐射和化学药物暴露均导致lncRNA表达发生特定变化。然而,这种共同作用对于细胞对压力和生存的反应可能具有重要意义。进一步的研究将表明lncRNA是否是患者治疗监测中的有用工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df72/6315432/136a38a8f2c6/ncrna-04-00033-g001.jpg

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