ADAMTS2通过PI3K/Akt信号通路促进口腔鳞癌细胞转移和侵袭

ADAMTS2 Promotes Metastasis and Invasion of Oral Squamous Cell Carcinoma Through PI3K/Akt Signaling Pathway

目的通过GEO数据库筛选口腔鳞癌相关的差异表达mRNA,并通过体外功能实验明确ADAMTS2对口腔鳞癌转移的作用及机制。方法运用GEO2R对两个表达谱进行差异基因分析,通过String构建PPI网络,利用Cytoscape中的Hubba和Mcode插件筛选关键基因,并通过GEPIA和Kaplan-Meier Plotter对筛选到的重要基因进行表达量和生存曲线的分析。随后,选定ADAMTS2作为研究主题,通过LinkedOmic数据库对ADAMTS2相关联的基因进行识别,并对Top 50正负相关基因进行功能富集分析。最后,通过体外实验对ADAMTS2在口腔鳞癌细胞中的功能进行验证。结果在细胞迁移和侵袭实验中,过表达ADAMTS2的SCC15和HSC3细胞迁移和侵袭能力高于对照组,敲低ADAMTS2则降低了口腔鳞癌细胞的迁移、侵袭能力;OSCC中的差异表达基因与ADAMTS2呈正相关;Top 50与ADAMTS2相关的基因主要与IL-17信号通路、细胞迁移的正向调节、血管生成的调节以及糖原代谢过程相关;ADAMTS2通过PI3K-Akt促进口腔鳞状细胞癌(OSCC)的糖酵解,进而促进OSCC细胞的转移和侵袭。结论ADAMTS2可能是OSCC转移和不良预后的潜在关键基因。

Objective To screen differentially expressed transcriptional RNAs related to oral squamous cell carcinoma through the GEO database,and to clarify the mechanism of ADAMTS2’s effect on oral squamous cell carcinoma metastasis through in vitro functional experiments.Methods GEO2Rwas used to perform differential gene analysis on two expression profiles.A PPI network was constructed using String,and key genes were screened using the Hubba and Mcode plugins in Cytoscape.The expression levels and survival curves of the selected important genes were analyzed using GEPIA and Kaplan Meier Plotter.Subsequently,ADAMTS2was selected as the research topic,and the genes associated with ADAMTS2were identified through the LinkedOmic database,and functional enrichment analysis was performed on the Top 50positive and negative correlation genes.Finally,the function of ADAMTS2was validated through in vitro experiments.Results In the experiment of cell migration and invasion,the migration and invasion ability of overexpression ADAMTS2in SCC15cell line was higher than that of negative control group;ADAMTS2in OSCC showed a positive correlation;Top 50and ADAMTS2related genes were mainly related to IL-17signaling pathway,positive regulation of cell migration,regulation of angiogenesis and glycogen metabolism;ADAMTS2promoted the glycolysis of oral squamous cell carcinoma(OSCC)through PI3K/Akt,thereby promoting the metastasis and invasion of OSCC cells.Conclusion ADAMTS2may be a potential gene accounting for OSCC metastasis and poor prognosis.