Knockdown of pseudogene derived from lncRNA DUXAP10 inhibits cell proliferation, migration, invasion, and promotes apoptosis in pancreatic cancer

J Cell Biochem. 2018 Apr;119(4):3671-3682. doi: 10.1002/jcb.26578. Epub 2018 Jan 5.

Abstract

Current evidence suggests that pseudogene derived lncRNAs may be important players in human cancer progression. Our previous study showed that DUXAP10 could promote cell proliferation in colorectal cancer. However, the clinical significance and potential role of DUXAP10 in human pancreatic cancer (PC) has not been uncovered. In this study, we found that DUXAP10 was overexpressed in PC tissues compared with normal tissues. DUXAP10 expression was significantly higher in patients with an advanced TNM stage and positive lymph node metastasis. Bioinformatic analysis showed that cell cycle progression was increased in patients with high DUXAP10 expression. In vitro and in vivo assays of DUXAP10 alterations revealed a complex integrated phenotype affecting cell growth, apoptosis, migration, and invasion. Mechanistic studies revealed that DUXAP10 has a crucial role in G2/M arrest. We further showed that DUXAP10 regulated PC cell proliferation through interact with RNA-binding protein EZH2 and LSD1. Overall, our findings indicates that DUXAP10 is an oncogenic lncRNA that promotes PC proliferation and metastasis.

Keywords: DUXAP10; cell proliferation; lncRNA; pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology
  • Cell Survival / genetics
  • Cell Survival / physiology
  • Computational Biology
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Immunoprecipitation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / physiology
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • RNA, Long Noncoding