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

doi:10.52396/JUST-2021-0063

中国科学技术大学学报 ›› 2021, Vol. 51 ›› Issue (5): 360-368.DOI: 10.52396/JUST-2021-0063

• 研究论文:生命科学与医学 • 上一篇下一篇

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

杨紫暄¹, 张雪寒¹, 申涛¹, 施荣华², 汪香婷^1*

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

收稿日期:2021-03-05 修回日期:2021-03-11 出版日期:2021-05-31 发布日期:2021-12-01
通讯作者: * E-mail:wangxt11@ustc.edu.cn

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

Yang Zixuan¹, Zhang Xuehan¹, Shen Tao¹, Shi Ronghua², Wang Xiangting^1*

1. Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China;
2. Core Facility Center for Life Sciences, School of Life Sciences, University of Science and Technology of China, Hefei 230026, China

Received:2021-03-05 Revised:2021-03-11 Online:2021-05-31 Published:2021-12-01
Contact: * E-mail: wangxt11@ustc.edu.cn

1. Supplementary data.rar(1223KB)

摘要/Abstract

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.

关键词: 碳酸酐酶抑制剂, U-104, CA9, CA12, 舌鳞状细胞癌

Abstract: 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.

Key words: carbonic anhydrase inhibitor, U-104, CA9, CA12, tongue squamous cell carcinoma

中图分类号:

R739.86

杨紫暄, 张雪寒, 申涛, 施荣华, 汪香婷. 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[J]. 中国科学技术大学学报, 2021, 51(5): 360-368.

YANG Zixuan, ZHANG Xuehan, SHEN Tao, SHI Ronghua, WANG Xiangting. Carbonic anhydrase inhibitor U-104 inhibits tumor progression through CA9 and CA12 in tongue squamous cell carcinoma[J]. Journal of University of Science and Technology of China, 2021, 51(5): 360-368.

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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

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