Comprehensive characterization of a drug-resistance-related ceRNA network across 15 anti-cancer drug categories.
Comprehensive characterization of a drug-resistance-related ceRNA network across 15 anti-cancer drug categories.
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跨 15 种抗癌药物类别的耐药相关 ceRNA 网络的综合表征
DOI：
10.1016/j.omtn.2021.02.011
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发表时间：
2021-06-04
期刊：
影响因子：
--
通讯作者：
Shang D
中科院分区：
文献类型：
--
作者：
Liu B;Zhou X;Wu D;Zhang X;Shen X;Mi K;Qu Z;Jiang Y;Shang D
癌症仍然是世界各地的一个主要健康问题。癌症治疗失败很大程度上归因于耐药性。竞争性内源性RNA（ceRNA）参与多种生物过程，从而影响癌症的药物敏感性。然而，尚未对药物敏感性相关 ceRNA 进行全面表征。在本研究中，我们构建了涵盖15种抗癌药物类别的15个ceRNA网络，涉及217个长非编码RNA（lncRNA）、158个microRNA（miRNA）和1,389个蛋白质编码基因（PCG）。我们发现这些 ceRNA 参与了一些标志性过程，例如“生长信号的自给自足”、“对抗生长信号不敏感”等等。然后，我们确定了跨 15 种抗癌药物类别的交叉 ceRNA 网络 (ICN)。通过分析共表达、蛋白质-蛋白质相互作用和转录因子-靶基因相互作用，我们进一步确定了 ICN 中的基因与临床可操作基因 (CAG) 之间的相互作用。我们发现 ICN 中的某些基因与 CAG 相关。最后，我们发现ICN中的基因在肿瘤中异常表达，其中一些基因与患者的生存时间和癌症分期相关。本研究构建了 15 个抗癌药物类别的 15 个 ceRNA 网络，并确定了一个交叉 ceRNA 网络 (ICN)。对 ICN 中基因的全面分析凸显了它们在癌症治疗中的潜在临床用途。
Cancer is still a major health problem around the world. The treatment failure of cancer has largely been attributed to drug resistance. Competitive endogenous RNAs (ceRNAs) are involved in various biological processes and thus influence the drug sensitivity of cancers. However, a comprehensive characterization of drug-sensitivity-related ceRNAs has not yet been performed. In the present study, we constructed 15 ceRNA networks across 15 anti-cancer drug categories, involving 217 long noncoding RNAs (lncRNAs), 158 microRNAs (miRNAs), and 1,389 protein coding genes (PCGs). We found that these ceRNAs were involved in hallmark processes such as “self-sufficiency in growth signals,” “insensitivity to antigrowth signals,” and so on. We then identified an intersection ceRNA network (ICN) across the 15 anti-cancer drug categories. We further identified interactions between genes in the ICN and clinically actionable genes (CAGs) by analyzing the co-expressions, protein-protein interactions, and transcription factor-target gene interactions. We found that certain genes in the ICN are correlated with CAGs. Finally, we found that genes in the ICN were aberrantly expressed in tumors, and some were associated with patient survival time and cancer stage. The present study constructed 15 ceRNA networks across 15 anti-cancer drug categories and identified an intersection ceRNA network (ICN). A comprehensive analysis of the genes in an ICN highlights their potential clinical utility in cancer therapy.
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