Integration of Transcriptomics and Metabolomics Reveals the Antitumor Mechanism Underlying Tadalafil in Colorectal Cancer.
Integration of Transcriptomics and Metabolomics Reveals the Antitumor Mechanism Underlying Tadalafil in Colorectal Cancer.
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DOI：
10.3389/fphar.2022.793499
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发表时间：
2022
影响因子：
5.6
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
--
作者：
Zhao, Pan;Shen, Yao;Li, Mengyang;Dan, Hanjun;Zhao, Zhiming;Zhang, Jian
已提出他达拉非（一种PDE 5抑制剂）在抗癌活性和延长生存期方面的潜在作用。然而，他达拉非在结直肠癌中的系统效应尚未完全了解。在这项研究中，我们评估了他达拉非在人结直肠癌细胞中的抗肿瘤活性。转录组学和代谢组学的整合为他达拉非诱导的抗肿瘤机制提供了一个系统的视角。我们发现，差异表达基因（DEG）主要涉及癌症中的microRNA、嘌呤代谢、鞘糖脂生物合成、精氨酸生物合成和氨基酸代谢。通过代谢组学分析，氨基酸代谢，尤其是丙氨酸、天冬氨酸和谷氨酸代谢是差异积累代谢物（DAMs）的主要部分。DEGs和DAMs的联合分析表明，它们也主要参与丙氨酸、天冬氨酸和谷氨酸的代谢。氨基酸代谢相关基因GPT、GGT 5和达特在他达拉非治疗后显著降低。特别是丙氨酸、天冬氨酸和谷氨酸代谢紊乱可能是他达拉非抗肿瘤活性的主要机制。
The potential role of tadalafil, a PDE5 inhibitor, in anticancer activity and prolonged survival has been proposed. However, the systematic effects of tadalafil in colorectal cancer were not fully understood. In this study, we assessed the anti-tumor activity of tadalafil in human colorectal cancer cells. A systematic perspective of the tadalafil-induced anti-tumor mechanism was provided by the integration of transcriptomics and metabolomics. We found that differentially expressed genes (DEGs) were mainly involved in microRNAs in cancer, purine metabolism, glycosphingolipid biosynthesis, arginine biosynthesis, and amino acid metabolism. Amino acid metabolism, especially alanine, aspartate, and glutamate metabolism was the most of the differentially accumulated metabolites (DAMs) through the analysis of metabolomics. The conjoint analysis of DEGs and DAMs presented that they were also mainly involved in alanine, aspartate, and glutamate metabolism. Amino acid metabolism-related genes, GPT, GGT5, and TAT, were significantly decreased after tadalafil treatment. In particular, the disturbance of alanine, aspartate, and glutamate metabolism may be the explanation for the major mechanism resulting from tadalafil anti-tumor activity.
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影响因子：
6.2
作者：
Dillon, BJ;Prieto, VG;Clark, MA
通讯作者：
Clark, MA
影响因子：
3.6
作者：
Roberts, Jane L.;Booth, Laurence;Dent, Paul
通讯作者：
Dent, Paul
影响因子：
7.2
作者：
Hassel JC;Jiang H;Bender C;Winkler J;Sevko A;Shevchenko I;Halama N;Dimitrakopoulou-Strauss A;Haefeli WE;Jäger D;Enk A;Utikal J;Umansky V
通讯作者：
Umansky V
DOI：
10.1073/pnas.1416498111
发表时间：
2014-10-14
影响因子：
11.1
作者：
Ammirante, Massimo;Shalapour, Shabnam;Karin, Michael
通讯作者：
Karin, Michael
影响因子：
8.8
作者：
Farshidfar, Farshad;Weljie, Aalim M.;Kopciuk, Karen A.;Hilsden, Robert;McGregor, S. Elizabeth;Buie, W. Donald;MacLean, Anthony;Vogel, Hans J.;Bathe, Oliver F.
通讯作者：
Bathe, Oliver F.