Zhang Xuesong, Liu Yakun, He Shengteng, Bi Liangjia, Liu Bing
Department of Stomatology, The 962nd Hospital of the PLA Joint Logistic Support Force, Harbin, China.
Department of Stomatology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.
IET Syst Biol. 2025 Jan-Dec;19(1):e12113. doi: 10.1049/syb2.12113. Epub 2024 Dec 23.
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.
口腔鳞状细胞癌（OSCC）是一种常见的头颈部恶性肿瘤，发病率高且预后较差。三氧化二砷（ATO）对实体瘤具有治疗作用。微波消融（MWA）在实体瘤治疗中具有独特优势。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。分别用ATO和/或MWA处理荷Cal-27细胞的裸鼠。采用RNA测序获得经ATO或MWA处理的小鼠肿瘤组织中的基因表达谱。RNA测序结果通过实时聚合酶链反应（PCR）进行验证。基于竞争性内源RNA（ceRNA）理论构建lncRNA-miRNA-mRNA共表达网络。使用差异表达基因进行基因本体论和京都基因与基因组百科全书分析。评估ATO和MWA对OSCC的联合作用。最后，进行CCK-8检测、EdU检测和transwell迁移检测，以检测HSPA6对OSCC细胞增殖和迁移的影响。在ATO处理组和MWA处理组中均观察到肿瘤组织体积减小。ATO组减小了37.8%，MWA组减小了35.0%。在ATO组中总共鉴定出207个差异表达的mRNA和lncRNA，在MWA组中总共鉴定出200个差异表达的mRNA和522个lncRNA。通过实时PCR验证了8个基因的表达水平。差异表达基因与“化学致癌作用”、“单纯疱疹感染”、“卟啉和叶绿素代谢”以及“MAPK信号通路”密切相关。构建了lncRNA-miRNA-mRNA共表达网络。ATO和MWA联合治疗对OSCC的抑制作用优于单独使用它们中的任何一种。ATO和MWA的协同作用与HSPA6的上调有关。HSPA6的下调可促进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具有协同作用，这与HSPA6的上调有关。
