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

Xu Wenqin; Ye Jingjing; Chen Tianbing

doi:10.24920/003966

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

Chinese Medical Sciences Journal Vol. 37, Issue 1, Pages: 31-43(2022)

Original Article | Updated：2024-04-10

- Identifying and Validating a Novel miRNA-mRNA Regulatory Network Associated with Prognosis in Lung Adenocarcinoma
- Affiliations：
  
  1. 1Central Laboratory, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241002, China
  2. 2Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu, Anhui 241002, China
- Author bio：
  
  *E-mail: Tianbing Chen, TianbingChen1987@wnmc.edu.cn.
- Funds：
- DOI：10.24920/003966
  CLC：
- Received：08 July 2021，
  
  Accepted：2021-11-30，
  
  Published Online：08 March 2022，
  
  Published：31 March 2022
- Accepted：
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Xu Wenqin, Ye Jingjing, Chen Tianbing. Identifying and Validating a Novel miRNA-mRNA Regulatory Network Associated with Prognosis in Lung Adenocarcinoma[J]. Chinese medical sciences journal, 2022, 37(1): 31-43.
DOI：

Xu Wenqin, Ye Jingjing, Chen Tianbing. Identifying and Validating a Novel miRNA-mRNA Regulatory Network Associated with Prognosis in Lung Adenocarcinoma[J]. Chinese medical sciences journal, 2022, 37(1): 31-43. DOI： 10.24920/003966.

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。

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.

关键词

Keywords

references

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