The positive feedback loop FOXO3/CASC11/miR-498 promotes the tumorigenesis of non-small cell lung cancer

Biochem Biophys Res Commun. 2019 Nov 12;519(3):518-524. doi: 10.1016/j.bbrc.2019.08.136. Epub 2019 Sep 16.

Abstract

An increasing number of studies have indicated that long noncoding RNAs (lncRNAs) are involved in the regulation of non-small-cell lung cancer (NSCLC). Nevertheless, there are still numerous undiscovered mechanisms underlying this molecular regulation. Here, the results illustrated that CASC11 is overexpressed in NSCLC tumor tissues and cell lines, which is closely related to the clinical features of NSCLC and poor survival. In functional experiments, CASC11 was shown to promote proliferation and cycle progression and enhance NSCLC tumorigenesis. In mechanical investigations, CASC11 was shown to target the miR-498/FOXO3 axis via a canonical competing endogenous RNA (ceRNA). In return, the transcription factor FOXO3 targets the CASC11 promoter region, thereby accelerating its transcription. Our findings demonstrate a crucial role for CASC11 as an oncogene in promoting NSCLC. These results reveal that CASC11 might be a potential therapeutic target for NSCLC.

Keywords: CASC11; FOXO3; Non-small-cell lung cancer; miR-498.

MeSH terms

  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cells, Cultured
  • Forkhead Box Protein O3 / metabolism*
  • Humans
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / metabolism*

Substances

  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • MIRN498 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long noncoding RNA CASC11, human