circTP63 functions as a ceRNA to promote lung squamous cell carcinoma progression by upregulating FOXM1

Nat Commun. 2019 Jul 19;10(1):3200. doi: 10.1038/s41467-019-11162-4.

Abstract

Circular RNAs (circRNAs) are identified as vital regulators in a variety of cancers. However, the role of circRNA in lung squamous cell carcinoma (LUSC) remains largely unknown. Herein, we explore the expression profiles of circRNA and mRNA in 5 paired samples of LUSC. By analyzing the co-expression network of differentially expressed circRNAs and dysregulated mRNAs, we identify that a cell cycle-related circRNA, circTP63, is upregulated in LUSC tissues and its upregulation is correlated with larger tumor size and higher TNM stage in LUSC patients. Elevated circTP63 promotes cell proliferation both in vitro and in vivo. Mechanistically, circTP63 shares miRNA response elements with FOXM1. circTP63 competitively binds to miR-873-3p and prevents miR-873-3p to decrease the level of FOXM1, which upregulates CENPA and CENPB, and finally facilitates cell cycle progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Cycle / physiology
  • Cell Line, Tumor
  • Cell Proliferation
  • Centromere Protein A / metabolism
  • Centromere Protein B / metabolism
  • Disease Progression*
  • Female
  • Forkhead Box Protein M1 / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Male
  • Mice, Inbred BALB C
  • MicroRNAs
  • Middle Aged
  • Neoplasms, Experimental
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • RNA, Messenger / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptome
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Up-Regulation*

Substances

  • CENPA protein, human
  • CENPB protein, human
  • Centromere Protein A
  • Centromere Protein B
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • MIRN873 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA, Messenger
  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins