A Systematic Analysis Identifies Key Regulators Involved in Cell Proliferation and Potential Drugs for the Treatment of Human Lung Adenocarcinoma.
A Systematic Analysis Identifies Key Regulators Involved in Cell Proliferation and Potential Drugs for the Treatment of Human Lung Adenocarcinoma.
复制标题
系统分析确定了参与细胞增殖的关键调节因子和治疗人肺腺癌的潜在药物
DOI：
10.3389/fonc.2021.737152
复制
发表时间：
2021
影响因子：
4.7
通讯作者：
Lu L
中科院分区：
文献类型：
--
作者：
Wang K;Zhang M;Wang J;Sun P;Luo J;Jin H;Li R;Pan C;Lu L
肺腺癌是最常见的恶性肿瘤之一。以细胞周期和细胞分裂失调为例的异常细胞增殖是癌症最突出的标志之一，并导致复发、转移和对癌症治疗的抗性。然而，LUAD特异性基因调控和临床意义仍然不清楚。在此，通过使用来自LUAD和正常肺样品的组织和细胞，检测到434个增加和828个减少的具有生物学意义的基因，包括127个细胞周期相关基因（95个增加和32个减少）、66个细胞分裂相关基因（56个增加和10个减少）和81个细胞增殖相关基因（34个增加和47个减少）。其中，12个基因（TPX2、CENPF、BUB1、PLK1、KIF2C、AURKB、CDKN 3、BUB1B、HMGA 2、CDK1、ASPM和CKS1B）的表达增加，2个基因（TACC1和MYH10）的表达减少。重要的是，11个增加的基因中有2个（CDKN 3和CKS1B）（HMGA 2除外）是LUAD中以前未表征的基因，可能是预后标志物。PLK1可能是LUAD的一个有希望的治疗靶点。蛋白质相互作用网络分析表明，CDK1和CDC20是LUAD细胞增殖的枢纽基因，可能在LUAD细胞增殖中起重要作用。此外，转录调节网络分析表明，转录因子E2 F1可能是通过调节大多数细胞周期、细胞分裂和细胞增殖相关DEG的表达来控制LUAD细胞增殖的关键调节因子。最后，阿司他丁A、海司他酮、伏立诺他和美贝维林被确定为LUAD的四种潜在治疗药物。这项工作揭示了促进人类LUAD细胞增殖的关键调节因子，并确定了四种潜在的治疗策略。
Lung adenocarcinoma (LUAD) is one of the most common and malignant cancer types. Abnormal cell proliferation, exemplified by cell cycle and cell division dysregulation, is one of the most prominent hallmarks of cancer and is responsible for recurrence, metastasis, and resistance to cancer therapy. However, LUAD-specific gene regulation and clinical significance remain obscure. Here, by using both tissues and cells from LUAD and normal lung samples, 434 increased and 828 decreased genes of biological significance were detected, including 127 cell cycle-associated genes (95 increased and 32 decreased), 66 cell division-associated genes (56 increased and 10 decreased), and 81 cell proliferation-associated genes (34 increased and 47 decreased). Among them, 12 increased genes (TPX2, CENPF, BUB1, PLK1, KIF2C, AURKB, CDKN3, BUB1B, HMGA2, CDK1, ASPM, and CKS1B) and 2 decreased genes (TACC1 and MYH10) were associated with all the three above processes. Importantly, 2 (CDKN3 and CKS1B) out of the 11 increased genes (except HMGA2) are previously uncharacterized ones in LUAD and can potentially be prognostic markers. Moreover, PLK1 could be a promising therapeutic target for LUAD. Besides, protein–protein interaction network analysis showed that CDK1 and CDC20 were the hub genes, which might play crucial roles in cell proliferation of LUAD. Furthermore, transcriptional regulatory network analysis suggested that the transcription factor E2F1 could be a key regulator in controlling cell proliferation of LUAD via expression modulation of most cell cycle-, cell division-, and cell proliferation-related DEGs. Finally, trichostatin A, hycanthone, vorinostat, and mebeverine were identified as four potential therapeutic agents for LUAD. This work revealed key regulators contributing to cell proliferation in human LUAD and identified four potential therapeutic agents for treatment strategy.
登录
查看更多内容
影响因子：
3.1
作者：
Bai, Yuquan;Xiong, Lecai;Tang, Hexiao
通讯作者：
Tang, Hexiao
人胃癌细胞系HGC-27侧群细胞的初步研究
影响因子：
1.1
作者：
Gao, Ganglong;Sun, Zhenliang;Zhang, Xueli
通讯作者：
Zhang, Xueli
影响因子：
5.7
作者：
Hsiao, Yung-Ting;Fan, Ming-Jen;Chung, Jing-Gung
通讯作者：
Chung, Jing-Gung
影响因子：
14.9
作者：
Han H;Cho JW;Lee S;Yun A;Kim H;Bae D;Yang S;Kim CY;Lee M;Kim E;Lee S;Kang B;Jeong D;Kim Y;Jeon HN;Jung H;Nam S;Chung M;Kim JH;Lee I
通讯作者：
Lee I
DOI：
10.1093/bioinformatics/btn615
发表时间：
2009-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Carbon S;Ireland A;Mungall CJ;Shu S;Marshall B;Lewis S;AmiGO Hub;Web Presence Working Group
通讯作者：
Web Presence Working Group