The lncRNA RUNX1-IT1 regulates C-FOS transcription by interacting with RUNX1 in the process of pancreatic cancer proliferation, migration and invasion

Cell Death Dis. 2020 Jun 2;11(6):412. doi: 10.1038/s41419-020-2617-7.

Abstract

Numerous long noncoding RNAs (lncRNAs) are aberrantly expressed in pancreatic cancer (PC); however, their functions and mechanisms in cancer progression are largely unknown. In this study, we identified a novel PC-associated lncRNA, RUNX1-IT1, that was significantly upregulated in PC patient samples from multiple centers and associated with poor prognosis. In vitro and in vivo, alterations in RUNX1-IT1 expression markedly affected PC proliferation, migration and invasion. RUNX1-IT1 contributed to the progression of PC by interacting with the adjacent gene RUNX1. Rescue experiments showed that RUNX1 reduced the cancer-promoting effect of RUNX1-IT1. RNA-seq analysis after silencing RUNX1-IT1 and RUNX1 highlighted alterations in the common target C-FOS. Mechanistically, we demonstrated that RUNX1-IT1 was a trans-acting factor that participated in the proliferation, migration and invasion of PC by recruiting RUNX1 to the C-FOS gene promoter. Furthermore, RUNX1-IT1 enhanced the transcription of the RUNX1 gene, indicating its potential as a cis-regulatory RNA involved in the upstream regulation of RUNX1. Overall, RUNX1-IT1 is a crucial oncogenic lncRNA that activates C-FOS expression by regulating and recruiting RUNX1 and is a potential prognostic biomarker and therapeutic target for PC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics
  • Core Binding Factor Alpha 2 Subunit / metabolism*
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology*
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Proto-Oncogene Proteins c-fos / genetics*
  • Proto-Oncogene Proteins c-fos / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Transcription, Genetic*
  • Up-Regulation / genetics

Substances

  • Core Binding Factor Alpha 2 Subunit
  • Proto-Oncogene Proteins c-fos
  • RNA, Long Noncoding
  • RUNX1 protein, human
  • RUNX1-IT1 long non-coding RNA, human