High circ-SEC31A expression predicts unfavorable prognoses in non-small cell lung cancer by regulating the miR-520a-5p/GOT-2 axis

Aging (Albany NY). 2020 Jun 4;12(11):10381-10397. doi: 10.18632/aging.103264. Epub 2020 Jun 4.

Abstract

Dysregulation of circular RNAs (circRNAs) has recently been shown to play important regulatory roles in cancer development and progression, including non-small cell lung cancer (NSCLC). However, the roles of most circRNAs in NSCLC are still unknown. In this study, we found that hsa_circ_0001421 (circ-SEC31A) was upregulated in NSCLC tissues and cell lines. Increased circ-SEC31A expression in NSCLC was significantly correlated with malignant characteristics and served as an independent risk factor for the post-surgical overall survival of NSCLC patients. Reduced circ-SEC31A expression in NSCLC decreased tumor cell proliferation, migration, invasion, and malate-aspartate metabolism. Mechanistically, we demonstrated that silencing circ-SEC31A downregulated GOT-2 expression by relieving the sponging effect of miR-520a-5p, which resulted in significantly reduced malate-aspartate metabolism in NSCLC cells. Taken together, these results revealed the important role of circ-SEC31A in the proliferation, migration, invasion, and metabolic regulation of NSCLC cells, providing a new perspective on circRNAs in NSCLC progression.

Keywords: GOT-2; hsa_circ_0001421 (circ-SEC31A); miR-520a-5p; non-small cell lung cancer; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Aspartate Aminotransferase, Mitochondrial / genetics*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Lung / pathology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Prognosis
  • RNA, Circular / metabolism*
  • RNA-Seq
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • MIRN520 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Aspartate Aminotransferase, Mitochondrial