Circular RNA circ-SLC7A6 acts as a tumor suppressor in non-small cell lung cancer through abundantly sponging miR-21

Cell Cycle. 2020 Sep;19(17):2235-2246. doi: 10.1080/15384101.2020.1806449. Epub 2020 Aug 14.

Abstract

Circular RNA (circRNA) is currently considered to be a key regulatory molecule in cancer biology. In the present study, we aimed to explore the functional and clinical roles of circ-SLC7A6 (a circRNA derived from SLC7A6 gene) in non-small cell lung cancer (NSCLC). Circ-SLC7A6 was significantly downregulated in NSCLC tissues in comparison to para-carcinoma tissues. Low circ-SLC7A6 was closely associated with larger tumor size, lymph node metastasis, advanced clinical stage and adverse outcome. Exogenous expression of circ-SLC7A6 evidently inhibited the proliferation and invasion of NSCLC cells. Further investigations revealed that miR-21 was the direct functional target of circ-SLC7A6, in which circ-SLC7A6 abundantly sponged miR-21 and elevated a cohort of tumor suppressors, thus inhibiting NSCLC progression. Interestingly, QKI, elevated by circ-SLC7A6, could directly bind to the introns flanking circ-SLC7A6 to facilitate circ-SLC7A6 production. Importantly, in vivo xenograft tumor experiments showed that reintroduction of circ-SLC7A6 retarded tumor growth as well as decreased lung metastatic nodules. Overall, our study demonstrates that circ-SLC7A6 is a novel tumor suppressor in NSCLC, targeting circ-SLC7A6/miR-21 axis may be a promising treatment for NSCLC patients.

Keywords: Circular RNA; miRNA; non-small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • RNA-Binding Proteins / metabolism

Substances

  • MIRN21 microRNA, human
  • MicroRNAs
  • QKI protein, human
  • RNA, Circular
  • RNA-Binding Proteins

Grants and funding

The work was funded by Education Scientific Research Fund “Young Seedlings” Project of Liaoning Provincial Department (QN2019015).