Chinese Medical Sciences Journal ›› 2022, Vol. 37 ›› Issue (1): 31-43.doi: 10.24920/003966

• 论著 • 上一篇    下一篇

鉴定并验证与肺腺癌预后相关的新的miRNA-mRNA调节网络

徐文琴1,2,叶静静1,2,陈天兵1,2,*()   

  1. 1皖南医学院弋矶山医院中心实验室,安徽 芜湖 241002,中国
    2皖南医学院重大疾病非编码RNA转化研究安徽普通高校重点实验室,安徽 芜湖 241002,中国
  • 收稿日期:2021-07-08 接受日期:2021-11-30 出版日期:2022-03-31 发布日期:2022-03-08
  • 通讯作者: 陈天兵 E-mail:tianbingchen1987@wnmc.edu.cn

Identifying and Validating a Novel miRNA-mRNA Regulatory Network Associated with Prognosis in Lung Adenocarcinoma

Wenqin Xu1,2,Jingjing Ye1,2,Tianbing Chen1,2,*()   

  1. 1Central Laboratory, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241002, China
    2Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu, Anhui 241002, China
  • Received:2021-07-08 Accepted:2021-11-30 Published:2022-03-31 Online:2022-03-08
  • Contact: Tianbing Chen E-mail:tianbingchen1987@wnmc.edu.cn

摘要:

目的 许多研究揭示了miRNA在多种人类癌症中的关键作用,包括肺腺癌(LUAD)。本研究试图探索与LUAD预后相关的新的miRNA-mRNA对。
方法 采用生物信息学工具(如OncomiR、StarBase、miRnet、GEPIA2和UALCAN)鉴定并验证与肺腺癌预后相关的新的miRNA-mRNA调节网络。
结果 首先,通过在OncomiR和StarBase中的表达和预后价值分析后得到了20个关键miRNA。在miRnet中预测了这些关键miRNAs的靶向mRNAs,并分别在GEPIA2和UALCAN中分析了它们的预后价值和表达模式。在StarBase中进行进一步的表达相关性分析。随后构建了一个新的miRNA-mRNA网络,其中每个RNA对都显示出负的表达相关性、相反的表达模式和预后价值。基于这些mRNAs构建了蛋白质相互作用网络,并从中确定了19个枢纽基因。富集分析表明“Cell Cycle,Mitotic”是最显著的富集项。然后,构建了miRNA-hub基因网络,选择并验证了一些miRNA-hub基因对的调节关系,包括hsa-miR-1976/RFC2、hsa-let-7c-5p/RFC2、hsa-let-7c-5p/ESPL1、hsa-let-7c-5p/CDC25A和hsa-miR-101-3p/KIF2C。此外,hsa-miR-1976和hsa-let-7c-5p的过表达还导致显著的细胞周期停滞。
结论 我们的结果确定了新的预后相关的miRNA-mRNA对,进一步阐明了miRNA-mRNA网络影响LUAD预后的分子调控机制。

关键词: 肺腺癌, 生物信息学分析, miRNA, 预后, 细胞周期

Abstract:

Objective Many studies have revealed the crucial roles of miRNA in multiple human cancers, including lung adenocarcinoma (LUAD). In this study, we sought to explore new miRNA-mRNA pairs that are associated with LUAD prognosis.
Methods A novel miRNA-mRNA regulatory network associated with prognosis in LUAD was identified and validated using the bioinformatic tools including OncomiR database, StarBase, miRnet, GEPIA2, UALCAN.
Results Twenty key miRNAs were compiled after the analysis of the expression and prognostic value in OncomiR and StarBase. Targeted mRNAs of these key miRNAs were predicted in miRnet, and the resulting mRNAs were also analyzed for their prognostic values and expression patterns in GEPIA2 and UALCAN, respectively. Further expression correlation analysis was performed in StarBase. Subsequently, a new miRNA-mRNA network was built, of which each RNA pair showed negative expression correlation, opposite expression pattern, and prognostic value. Protein-protein interaction network was under construction for the mRNAs, and 19 hub genes were determined. Enrichment analysis showed that “Cell Cycle, Mitotic” was the most significantly enriched term. Then, a miRNA-hub gene sub-network was built. We selected and validated the regulatory relationship of some miRNA-hub pairs, including hsa-miR-1976/RFC2, hsa-let-7c-5p/RFC2, hsa-let-7c-5p/ESPL1, hsa-let-7c-5p/CDC25A, and hsa-miR-101-3p/KIF2C. Moreover, over-expression of hsa-miR-1976 and hsa-let-7c-5p resulted in significant cell cycle arrest.
Conclusions Our results determined new prognosis-associated miRNA-mRNA pairs and might shed further light on the mechanism via which miRNA-mRNA network influences prognosis in LUAD.

Key words: lung adenocarcinoma, bioinformatic analysis, miRNA, prognosis, cell cycle

基金资助: 国家自然科学基金(81901519);安徽省自然科学基金(1908085QH380);皖南医学院弋矶山医院人才引进项目(YR201901)

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