Liu Bing, Zhou Xiaorui, Wu Dongyuan, Zhang Xuesong, Shen Xiuyun, Mi Kai, Qu Zhangyi, Jiang Yanan, Shang Desi
Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University, Harbin 150081, P.R. China.
Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin 150086, P.R. China.
Mol Ther Nucleic Acids. 2021 Feb 15;24:11-24. doi: 10.1016/j.omtn.2021.02.011. eCollection 2021 Jun 4.
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.
癌症仍然是全球主要的健康问题。癌症治疗失败在很大程度上归因于耐药性。竞争性内源性RNA（ceRNA）参与各种生物学过程，从而影响癌症的药物敏感性。然而，尚未对与药物敏感性相关的ceRNA进行全面表征。在本研究中，我们构建了跨越15种抗癌药物类别的15个ceRNA网络，涉及217个长链非编码RNA（lncRNA）、158个微小RNA（miRNA）和1389个蛋白质编码基因（PCG）。我们发现这些ceRNA参与了诸如“生长信号的自我充足”“对生长抑制信号不敏感”等标志性过程。然后，我们确定了跨越15种抗癌药物类别的交集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，其中一些与患者生存时间和癌症分期相关。
