Senescence-associated genes and non-coding RNAs function in pancreatic cancer progression

RNA Biol. 2020 Nov;17(11):1693-1706. doi: 10.1080/15476286.2020.1719752. Epub 2020 Jan 30.

Abstract

Pancreatic cancer is a major cause of mortality with a poor diagnosis and prognosis that most often occurs in elderly patients. Few studies, however, focus on the interplay of age and pancreatic cancer at the transcriptional level. Here we evaluated the possible roles of age-dependent, differentially expressed genes (DEGs) in pancreatic cancer. These DEGs were used to construct a correlation network and clustered in six gene modules, among which two modules were highly correlated with patients' survival time. Integrating different datasets, including ATAC-Seq and ChIP-Seq, we performed multi-parallel analyses and identified eight age-dependent protein coding genes and two non-coding RNAs as potential candidates. These candidates, together with KLF5, a potent functional transcription factor in pancreatic cancer, are likely to be key elements linking cellular senescence and pancreatic cancer, providing insights on the balance between them, as well as on diagnosis and subsequent prognosis of pancreatic cancer.

Keywords: RNA-Seq; Senescence; gene Module; non-coding RNA; pancreatic Cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Biomarkers, Tumor*
  • Cell Proliferation
  • Computational Biology / methods
  • Disease Progression
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks
  • Humans
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Neoplasms / therapy
  • RNA, Long Noncoding / genetics*
  • Transcription Factors / metabolism

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • Transcription Factors

Grants and funding

This work was supported by the Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology [2014FXCX009]; National Natural Science Foundation of China [91540107].