ELAVL4 promotes the tumorigenesis of small cell lung cancer by stabilizing LncRNA LYPLAL1-DT and enhancing profilin 2 activation

FASEB J. 2023 Oct;37(10):e23170. doi: 10.1096/fj.202300314RR.

Abstract

Small cell lung cancer (SCLC) is one of the most malignant tumors that has an extremely poor prognosis. RNA-binding protein (RBP) and long noncoding RNA (lncRNA) have been shown to be key regulators during tumorigenesis as well as lung tumor progression. However, the role of RBP ELAVL4 and lncRNA LYPLAL1-DT in SCLC remains unclear. In this study, we verified that lncRNA LYPLAL1-DT acts as an SCLC oncogenic lncRNA and was confirmed in vitro and in vivo. Mechanistically, LYPLAL1-DT negatively regulates the expression of miR-204-5p, leading to the upregulation of PFN2, thus, promoting SCLC cell proliferation, migration, and invasion. ELAVL4 has been shown to enhance the stability of LYPLAL1-DT and PFN2 mRNA. Our study reveals a regulatory pathway, where ELAVL4 stabilizes PFN2 and LYPLAL1-DT with the latter further increasing PFN2 expression by blocking the action of miR-204-5p. Upregulated PFN2 ultimately promotes tumorigenesis and invasion in SCLC. These findings provide novel prognostic indicators as well as promising new therapeutic targets for SCLC.

Keywords: ELAVL4; lncRNA LYPLAL1-DT; profilin 2; small cell lung cancer; tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinogenesis / genetics
  • Cell Transformation, Neoplastic / genetics
  • ELAV-Like Protein 4
  • Humans
  • Lung Neoplasms* / genetics
  • MicroRNAs* / genetics
  • Profilins / genetics
  • RNA, Long Noncoding* / genetics
  • Small Cell Lung Carcinoma* / genetics

Substances

  • RNA, Long Noncoding
  • Profilins
  • MicroRNAs
  • ELAVL4 protein, human
  • ELAV-Like Protein 4
  • PFN2 protein, human
  • MIRN204 microRNA, human