【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
【机 构】
：
中国科学技术大学生命科学与医学部,安徽合肥230026;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
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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.
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