Corrà Fabio, Agnoletto Chiara, Minotti Linda, Baldassari Federica, Volinia Stefano
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
Front Oncol. 2018 Aug 29;8:327. doi: 10.3389/fonc.2018.00327. eCollection 2018.
Non-coding RNAs (ncRNAs) have been implicated in most cellular functions. The disruption of their function through somatic mutations, genomic imprinting, transcriptional and post-transcriptional regulation, plays an ever-increasing role in cancer development. ncRNAs, including notorious microRNAs, have been thus proposed to function as tumor suppressors or oncogenes, often in a context-dependent fashion. In parallel, ncRNAs with altered expression in cancer have been reported to exert a key role in determining drug sensitivity or restoring drug responsiveness in resistant cells. Acquisition of resistance to anti-cancer drugs is a major hindrance to effective chemotherapy and is one of the most important causes of relapse and mortality in cancer patients. For these reasons, non-coding RNAs have become recent focuses as prognostic agents and modifiers of chemo-sensitivity. This review starts with a brief outline of the role of most studied non-coding RNAs in cancer and then highlights the modulation of cancer drug resistance via known ncRNAs based mechanisms. We identified from literature 388 ncRNA-drugs interactions and analyzed them using an unsupervised approach. Essentially, we performed a network analysis of the non-coding RNAs with direct relations with cancer drugs. Within such a machine-learning framework we detected the most representative ncRNAs-drug associations and groups. We finally discussed the higher integration of the drug-ncRNA clusters with the goal of disentangling effectors from downstream effects and further clarify the involvement of ncRNAs in the cellular mechanisms underlying resistance to cancer treatments.
非编码RNA（ncRNAs）参与了大多数细胞功能。通过体细胞突变、基因组印记、转录和转录后调控对其功能的破坏在癌症发展中发挥着越来越重要的作用。因此，包括臭名昭著的微小RNA在内的ncRNAs被认为可作为肿瘤抑制因子或癌基因发挥作用，且通常依赖于具体环境。与此同时，据报道在癌症中表达改变的ncRNAs在决定药物敏感性或恢复耐药细胞的药物反应性方面发挥着关键作用。获得抗癌药物耐药性是有效化疗的主要障碍，也是癌症患者复发和死亡的最重要原因之一。基于这些原因，非编码RNA最近已成为作为预后指标和化疗敏感性调节剂的研究热点。本综述首先简要概述了研究最多的非编码RNA在癌症中的作用，然后重点介绍了通过已知的基于ncRNAs的机制对癌症耐药性的调节。我们从文献中确定了388种ncRNA-药物相互作用，并使用无监督方法对其进行了分析。本质上，我们对与癌症药物有直接关系的非编码RNA进行了网络分析。在这样一个机器学习框架内，我们检测到了最具代表性的ncRNA-药物关联和组。我们最后讨论了药物-ncRNA簇的更高整合，目的是从下游效应中分离出效应器，并进一步阐明ncRNAs在癌症治疗耐药性潜在细胞机制中的作用。
