碳酸酐酶抑制剂U-104通过CA9和CA12抑制舌鳞状细胞癌的进程  

Carbonic anhydrase inhibitor U-104 inhibits tumor progression through CA9 and CA12 in tongue squamous cell carcinoma

作　　者：杨紫暄 张雪寒 申涛 施荣华[2] 汪香婷 Yang Zixuan;Zhang Xuehan;Shen Tao;Shi Ronghua;Wang Xiangting(Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230026,China;Core Facility Center for Life Sciences,School of Life Sciences,University of Science and Technology of China,Hefei 230026,China)

机构地区：[1]中国科学技术大学生命科学与医学部,安徽合肥230026 [2]中国科学技术大学生命科学学院综合仪器实验中心,安徽合肥230026

出　　处：《中国科学技术大学学报》2021年第5期360-368,共9页JUSTC

基　　金：supported by the National Natural Science Foundation of China(31970598);the Fundamental Research Funds for the Central Universities(YD2070002010).

摘　　要：U-104是一类高效的碳酸酐酶(CA)抑制剂,有望作为潜在的抗肿瘤药物应用于少数几类肿瘤的治疗.然而,U-104的下游机制及其在舌鳞状细胞癌中的功能尚不明确;其抗肿瘤效果是否依赖于CA9和CA12也未被证明.在本工作中,我们通过RNA测序发现了受U-104调节的差异表达基因和U-104可能影响的细胞内生物过程.在差异基因的富集分析中,排名位于前列的生物学过程包括与细胞死亡相关、细胞增殖、迁移和药物反应等生物学过程;这与我们利用U-104处理TSCC15舌癌细胞后观察到的生物学效应一致.进一步地,干扰CA9或CA12的表达完全消除了U-104对细胞迁移、死亡及关键差异基因表达的影响.总体而言,我们的研究在转录组水平提示了U-104的下游调节机制,并证明了在舌鳞状细胞癌中U-104的抗肿瘤功能依赖于CA9和CA12.此工作拓展了现阶段人们对于U-104抗肿瘤功能的认知,并提供了一类针对舌鳞状细胞癌的潜在治疗方法.U-104,an effective inhibitor of carbonic anhydrases(CAs),has been shown as a potential anti-tumor drug in several human cancer types.However,the downstream mechanisms of U-104 and its functions in tongue squamous cell carcinoma(TSCC)remain unclear.It is neither confirmed that whether the anti-tumor effects of U-104 are dependent on CA9 and CA12.In this work,we found differentially expressed genes(DEGs)and potential cellular processes regulated by U-104 through RNA sequencing.The cell death-related,cell proliferation,migration and response to drug cellular processes were among the top GO(gene ontology)processes,which were consistent with the observed biological effects upon U-104 treatment in TSCC15 cells.Furthermore,knockdown(KD)of CA9 or CA12 completely eliminated the U-104 effects on the cell migration,cell death,and the expression of critical DEGs.All together,our study suggests the regulatory mechanisms of U-104 at the transcriptome level and demonstrates the anti-tumor functions of U-104 dependent on CA9 and CA12 in TSCC.Our findings expand the current knowledge on the anti-tumor functions of U-104 and provide a potential therapeutic option for TSCC.

关 键 词：碳酸酐酶抑制剂 U-104 CA9 CA12 舌鳞状细胞癌 

分 类 号：R739.86[医药卫生—肿瘤]