Analysis of lncRNA-mRNA networks after MEK1/2 inhibition based on WGCNA in pancreatic ductal adenocarcinoma

J Cell Physiol. 2020 Apr;235(4):3657-3668. doi: 10.1002/jcp.29255. Epub 2019 Oct 3.

Abstract

Pancreatic ductal adenocarcinoma (PDA) responds poorly to treatment. Efforts have been exerted to prolong the survival time of PDA, but the 5-year survival rates remain disappointing. Understanding the molecular mechanisms of PDA development is significant. MEK/ERK pathway signaling has been proven to be important in PDA. lncRNA-mRNA networks have become a vital part of molecular mechanisms in the MEK/ERK pathway. Herein, weighted gene coexpression network analysis was used to investigate the coexpressed lncRNA-mRNA networks in the MEK/ERK pathway based on GSE45765. Differently expressed long noncoding RNA (lncRNA) and messenger RNA (mRNA) were found and 10 modules were identified based on coexpression profiles. Gene ontology and Kyoto Encyclopedia of Genes and Genomes were then performed to analyze the coexpressed lncRNA and mRNA in different modules. PDA cells and tissues were used to validate the analysis results. Finally, we found that NONHSAT185150.1 and B4GALT6 were negatively correlated with MEK1/2. By analyzing GSE45765, the genome-wide profiles of lncRNA-mRNA network after MEK1/2 was established, which might aid the development of drug-targeting MEK1/2 and the investigation of diagnostic markers.

Keywords: MEK1/2; WGCNA; lncRNA; pancreatic ductal adenocarcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Ontology / statistics & numerical data
  • Gene Regulatory Networks / genetics
  • Humans
  • MAP Kinase Kinase 1 / genetics
  • MAP Kinase Kinase 2 / genetics
  • MAP Kinase Signaling System / genetics
  • Male
  • RNA, Long Noncoding / classification
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / genetics*

Substances

  • RNA, Long Noncoding
  • RNA, Messenger
  • MAP2K2 protein, human
  • MAP Kinase Kinase 1
  • MAP Kinase Kinase 2
  • MAP2K1 protein, human