Circular RNA circ-PTEN elevates PTEN inhibiting the proliferation of non-small cell lung cancer cells

Hum Cell. 2021 Jul;34(4):1174-1184. doi: 10.1007/s13577-021-00526-y. Epub 2021 Apr 5.

Abstract

Phosphatase and tensin homolog (PTEN) is a well-known tumor suppressor in various cancer types, including non-small cell lung cancer (NSCLC). Circular RNA (circRNA) has recently been proven to be strongly linked with cancer progression. Here, we aimed to investigate the biological relevance and clinical significance of circRNA derived from PTEN in NSCLC. We found that circ-PTEN (hsa_circ_0094342) was significantly decreased in NSCLC tissues and serum, which was attributed to the upregulation of RNA-binding protein DHX9. Low circ-PTEN was linked with malignant clinical features and poor outcome. Exogenous expression of circ-PTEN markedly inhibited NSCLC cell proliferation in vitro as well as retarded tumor growth in vivo. Circ-PTEN increased the expression of its host gene PTEN via acting as a sponge for miR-155 and miR-330-3p, leading to the inactivation of the carcinogenic PI3K/AKT signaling pathway. The xenograft tumor model also indicated the existence of circ-PTEN/miR-155/miR-330-3p/PTEN regulatory axis in vivo. Our data for the first time demonstrate that circ-PTEN functions as a tumor-inhibiting circRNA in NSCLC through post-transcriptionally regulating PTEN, hinting a promising diagnostic/prognostic biomarker as well as therapeutic target for NSCLC patients.

Keywords: Biomarker; CircRNA; MiRNA sponge; NSCLC; PTEN.

MeSH terms

  • Biomarkers, Tumor
  • Carcinogenesis / genetics
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Female
  • Gene Expression*
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Male
  • MicroRNAs / metabolism
  • Middle Aged
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / metabolism
  • PTEN Phosphohydrolase / physiology*
  • Prognosis
  • RNA, Circular / physiology*

Substances

  • Biomarkers, Tumor
  • MIRN155 microRNA, human
  • MIRN330 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • PTEN Phosphohydrolase
  • PTEN protein, human