c-Myc-activated USP2-AS1 suppresses senescence and promotes tumor progression via stabilization of E2F1 mRNA

Cell Death Dis. 2021 Oct 27;12(11):1006. doi: 10.1038/s41419-021-04330-2.

Abstract

The c-Myc oncoprotein plays a prominent role in cancer initiation, progression, and maintenance. Long noncoding RNAs (lncRNAs) are recently emerging as critical regulators of the c-Myc signaling pathway. Here, we report the lncRNA USP2-AS1 as a direct transcriptional target of c-Myc. Functionally, USP2-AS1 inhibits cellular senescence and acts as an oncogenic molecule by inducing E2F1 expression. Mechanistically, USP2-AS1 associates with the RNA-binding protein G3BP1 and facilitates the interaction of G3BP1 to E2F1 3'-untranslated region, thereby leading to the stabilization of E2F1 messenger RNA. Furthermore, USP2-AS1 is shown as a mediator of the oncogenic function of c-Myc via the regulation of E2F1. Together, these findings suggest that USP2-AS1 is a negative regulator of cellular senescence and also implicates USP2-AS1 as an important player in mediating c-Myc function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Cellular Senescence
  • Disease Progression
  • E2F1 Transcription Factor / metabolism*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • RNA, Messenger / metabolism*
  • Salivary alpha-Amylases / metabolism*
  • Signal Transduction
  • Ubiquitin Thiolesterase / metabolism*

Substances

  • E2F1 Transcription Factor
  • RNA, Messenger
  • Amy1 protein, mouse
  • Salivary alpha-Amylases
  • Ubiquitin Thiolesterase
  • Usp2 protein, mouse