基于高通量测序的三氧化二砷和微波消融治疗口腔鳞状细胞癌的机制。

IF 1.9 4区 生物学 Q4 CELL BIOLOGY
Xuesong Zhang, Yakun Liu, Shengteng He, Liangjia Bi, Bing Liu
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引用次数: 0

摘要

口腔鳞状细胞癌(Oral squamous cell carcinoma, OSCC)是常见的头颈部恶性肿瘤,发病率高,预后差。三氧化二砷(ATO)对实体瘤有治疗作用。微波消融(MWA)在治疗实体肿瘤方面具有独特的优势。然而,ATO和MWA的治疗机制以及它们对OSCC的联合作用在很大程度上尚不清楚。携带Cal-27细胞的裸鼠分别用ATO和/或MWA处理。RNA测序获得ATO或MWA处理小鼠肿瘤组织中的基因表达谱。采用实时聚合酶链反应(real-time polymerase chain reaction, PCR)验证RNA测序结果。lncRNA-miRNA-mRNA共表达网络是基于竞争内源RNA (ceRNA)理论构建的。使用差异表达基因进行基因本体和京都基因与基因组百科全书分析。评价ATO和MWA对OSCC的联合作用。最后通过CCK-8法、EdU法和transwell迁移法检测HSPA6对OSCC细胞增殖和迁移的影响。ATO和mwa处理组肿瘤组织体积均减小。ATO组下降37.8%,MWA组下降35.0%。ATO组共鉴定出207和539个差异表达mrna和lncrna。在MWA组中共鉴定出200和522个差异表达mrna和lncrna。通过实时荧光定量PCR验证8个基因的表达水平。差异表达基因与“化学致癌”、“单纯疱疹感染”、“卟啉和叶绿素代谢”、“MAPK信号通路”密切相关。构建lncRNA-miRNA-mRNA共表达网络。ATO和MWA联合处理对OSCC的抑制作用优于两者。ATO和MWA的协同作用与HSPA6的上调有关。下调HSPA6可促进OSCC细胞的增殖和迁移。本研究检测了与OSCC治疗相关的长链非编码RNA和mRNA表达谱,并构建了相应的ceRNA网络。三氧化二砷和MWA对OSCC有协同作用,这与HSPA6的上调有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The mechanism of arsenic trioxide and microwave ablation in the treatment of oral squamous cell carcinoma based on high throughput sequencing.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignant tumour with high incidence and poor prognosis. Arsenic trioxide (ATO) has therapeutic effects on solid tumours. Microwave ablation (MWA) has unique advantages in the treatment of solid tumours. However, the therapeutic mechanism of ATO and MWA, as well as their combined effect on OSCC were largely unelucidated. Cal-27 cell-bearing nude mice were treated with ATO and/or MWA, respectively. RNA sequencing was used to obtain gene expression profiles in tumour tissues of mice treated by ATO or MWA. RNA sequencing results were verified by real-time polymerase chain reaction (PCR). The lncRNA-miRNA-mRNA co-expression network was constructed based on the competitive endogenous RNA (ceRNA) theory. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed using differentially expressed genes. The combined effect of ATO and MWA on OSCC was evaluated. Finally, CCK-8 assay, EdU assay and transwell migration assay were performed to detect the effect of HSPA6 on the proliferation and migration of OSCC cells. The reduced volume of tumour tissues was observed in both ATO- and MWA-treated groups. 37.8% decreased in the ATO group and 35.0% in the MWA group. A total of 207 and 539 differentially expressed mRNAs and lncRNAs were identified in the ATO group. And a total of 200 and 522 differentially expressed mRNAs and lncRNAs in the MWA group were identified. The expression levels of 8 genes were verified by real-time PCR. The differentially expressed genes were closely related to "chemical carcinogenesis", "herpes simplex infection", "porphyrin and chlorophyll metabolism", and "MAPK signalling pathway". The lncRNA-miRNA-mRNA co-expression networks were constructed. The combined treatment with ATO and MWA showed a better inhibitive effect on OSCC than either of them. The synergistic effect of ATO and MWA was related to the upregulation of HSPA6. The downregulation of HSPA6 could promote the proliferation and migration of OSCC cells. This study detected the long non-coding RNA and mRNA expression profiles related to the treatment of OSCC and constructed corresponding ceRNA networks. Arsenic trioxide and MWA have a synergistic effect on OSCC, which was related to the upregulation of HSPA6.

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来源期刊
IET Systems Biology
IET Systems Biology 生物-数学与计算生物学
CiteScore
4.20
自引率
4.30%
发文量
17
审稿时长
>12 weeks
期刊介绍: IET Systems Biology covers intra- and inter-cellular dynamics, using systems- and signal-oriented approaches. Papers that analyse genomic data in order to identify variables and basic relationships between them are considered if the results provide a basis for mathematical modelling and simulation of cellular dynamics. Manuscripts on molecular and cell biological studies are encouraged if the aim is a systems approach to dynamic interactions within and between cells. The scope includes the following topics: Genomics, transcriptomics, proteomics, metabolomics, cells, tissue and the physiome; molecular and cellular interaction, gene, cell and protein function; networks and pathways; metabolism and cell signalling; dynamics, regulation and control; systems, signals, and information; experimental data analysis; mathematical modelling, simulation and theoretical analysis; biological modelling, simulation, prediction and control; methodologies, databases, tools and algorithms for modelling and simulation; modelling, analysis and control of biological networks; synthetic biology and bioengineering based on systems biology.
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