Fang Shan, Wu Yuhao, Zhang Haiyan, Zeng Qingyu, Wang Peiru, Zhang Linglin, Yan Guorong, Zhang Guolong, Wang Xiuli
Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
Photodiagnosis Photodyn Ther. 2022 Sep;39:102907. doi: 10.1016/j.pdpdt.2022.102907. Epub 2022 May 13.
5-Aminolevulinic acid-based photodynamic therapy (ALA-PDT) is an effective therapy in treating inoperable cutaneous squamous cell carcinoma (cSCC) in China. However, its exact mechanism in treating cSCC is still unclear. Here, we analyzed expression profiles of lncRNAs and mRNAs of cSCC after ALA-PDT in a mouse model using Mouse Transcriptome Assay 1.0 chip. A total of 592 and 828 differentially expressed genes were identified in comparisons of ALA-PDT after 3 h vs. control, ALA-PDT after 6 h vs. control respectively. Regarding the lncRNAs analysis, a total of 185 and 410 differentially expressed lncRNAs were sought out. Bioinformatics analyses including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, pathway relation network, and gene set enrichment analysis revealed that the pathways of ALA-PDT in treating cSCC were mainly associated with immune regulation, NF-κB signaling pathway, TLR signaling pathway, PI3K-Akt signaling pathway, TNF signaling pathway, and MAPK signaling pathway, which was validated by western blot analysis. Furthermore, a lncRNA-mRNA co-expression network revealed 118 network pairs comprising 36 lncRNAs and 68 mRNAs. These findings provide a basis for investigations into the treatment mechanisms of ALA-PDT in treating cSCC.
基于5-氨基酮戊酸的光动力疗法（ALA-PDT）在中国是治疗不可切除性皮肤鳞状细胞癌（cSCC）的一种有效疗法。然而，其治疗cSCC的确切机制仍不清楚。在此，我们使用小鼠转录组分析1.0芯片分析了小鼠模型中ALA-PDT治疗后cSCC的lncRNA和mRNA表达谱。在ALA-PDT 3小时后与对照组、ALA-PDT 6小时后与对照组的比较中，分别共鉴定出592个和828个差异表达基因。关于lncRNA分析，共找出185个和410个差异表达的lncRNA。包括基因本体论、京都基因与基因组百科全书通路、通路关系网络和基因集富集分析在内的生物信息学分析表明，ALA-PDT治疗cSCC的通路主要与免疫调节、NF-κB信号通路、TLR信号通路、PI3K-Akt信号通路、TNF信号通路和MAPK信号通路相关，这通过蛋白质印迹分析得到了验证。此外，一个lncRNA-mRNA共表达网络揭示了由36个lncRNA和68个mRNA组成的118个网络对。这些发现为研究ALA-PDT治疗cSCC的机制提供了依据。
