The lncRNA ENSG00000254041.1 promotes cell invasiveness and associates with poor prognosis of pancreatic ductal adenocarcinoma

Aging (Albany NY). 2020 Feb 23;12(4):3647-3661. doi: 10.18632/aging.102835. Epub 2020 Feb 23.

Abstract

Pancreatic cancer (PC) mainly occurs after 60 years of age, and its prognosis remains poor despite modest improvements in recent decades. Long non-coding RNAs (lncRNAs) are well known as a class of transcripts involved in cancer occurrence and progression. The process of epithelial to a mesenchymal (EMT) phenotype in tumor cell increases their migratory and invasive properties, resulting in facilitating metastasis. Here, we reanalyzed RNA-seq data from the TCGA PC database and identified that ENSG00000254041.1 increasingly expressed in samples with elevated EMT signature score. Then, the evaluated expression and prognostic significance of ENSG00000254041.1 were verified in our cohort. Meanwhile, multivariate analysis suggested that ENSG00000254041.1 was independent factors for predicting the prognosis of PC, apart from advanced stage (III/IV). Moreover, functional assay revealed that knock down of ENSG00000254041.1 significantly decreased proliferation, invasion and chemoresistance of PC cells (SW1990 and BxPC-3), while overexpression of ENSG00000254041.1 in PC cells (Panc-1) resulted in the opposite effects. Western blot showed that knockdown of ENSG00000254041.1 expression in PC cells caused a significant downregulation of vimentin, Snail and SOX4, and upregulation of E-cadherin; also, ENSG00000254041.1 overexpression in PC cells resulted in opposite effects. In conclusion, these findings indicated that ENSG00000254041.1 promotes PC progression, and might provide a potential biomarker for predicting the prognosis of PC.

Keywords: LncRNA; chemoresistance; invasion; pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Databases, Factual
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Survival Rate

Substances

  • RNA, Long Noncoding