Department of Biology and Chemistry, College of Liberal Arts and Sciences, National University of Defense Technology, Changsha 410073, China.
Int J Mol Sci. 2022 Jun 8;23(12):6411. doi: 10.3390/ijms23126411.
The pivotal roles of miRNAs in carcinogenesis, metastasis, and prognosis have been demonstrated recently in various cancers. This study intended to investigate the specific roles of hsa-miR-654-5p in lung cancer, which is, in general, rarely discussed. A series of closed-loop bioinformatic functional analyses were integrated with in vitro experimental validation to explore the overall biological functions and pan-cancer regulation pattern of miR-654-5p. We found that miR-654-5p abundance was significantly elevated in LUAD tissues and correlated with patients' survival. A total of 275 potential targets of miR-654-5p were then identified and the miR-654-5p- regulation axis was validated in vitro as a proof of concept. Furthermore, we revealed the tumor-suppressing roles of miR-654-5p and demonstrated that miR-654-5p inhibited the lung cancer cell epithelial-mesenchymal transition (EMT) process, cell proliferation, and migration using target-based, abundance-based, and ssGSEA-based bioinformatic methods and in vitro validation. Following the construction of a protein-protein interaction network, 11 highly interconnected hub genes were identified and a five-genes risk scoring model was developed to assess their potential prognostic ability. Our study does not only provide a basic miRNA-mRNA-phenotypes reference map for understanding the function of miR-654-5p in different cancers but also reveals the tumor-suppressing roles and prognostic values of miR-654-5p.
miRNA 在癌症发生、转移和预后中的关键作用最近在各种癌症中得到了证实。本研究旨在探讨 hsa-miR-654-5p 在肺癌中的具体作用,而肺癌通常很少被讨论。本研究综合了一系列闭环生物信息学功能分析和体外实验验证,以探讨 miR-654-5p 的整体生物学功能和泛癌调控模式。我们发现 miR-654-5p 在 LUAD 组织中的丰度显著升高,并与患者的生存相关。然后鉴定了 275 个潜在的 miR-654-5p 靶标,并在体外验证了 miR-654-5p-调控轴作为概念验证。此外,我们揭示了 miR-654-5p 的肿瘤抑制作用,并通过靶标、丰度和 ssGSEA 基于生物信息学方法和体外验证证实了 miR-654-5p 抑制肺癌细胞上皮-间充质转化(EMT)过程、细胞增殖和迁移。在构建蛋白质-蛋白质相互作用网络后,鉴定了 11 个高度相互关联的枢纽基因,并开发了一个五基因风险评分模型来评估它们的潜在预后能力。我们的研究不仅为理解 miR-654-5p 在不同癌症中的功能提供了一个基本的 miRNA-mRNA-表型参考图谱,还揭示了 miR-654-5p 的肿瘤抑制作用和预后价值。