Downregulation of hsa_circ_0007580 inhibits non-small cell lung cancer tumorigenesis by reducing miR-545-3p sponging

Aging (Albany NY). 2020 Jul 18;12(14):14329-14340. doi: 10.18632/aging.103472. Epub 2020 Jul 18.

Abstract

Non-small cell lung cancer (NSCLC) is a highly malignant tumor. Many circular RNAs (circRNAs) are reportedly in regulating the progression of NSCLC. To identify potential therapeutic targets for NSCLC, we conducted a bioinformatics analysis of circRNAs differentially expressed between NSCLC tissues and adjacent normal tissues. Hsa_circ_0007580 was upregulated in NSCLC tumor tissues, and the expression of its host gene (protein kinase Ca) correlated negatively with overall survival. Short-hairpin RNAs were used to knock down hsa_circ_0007580 in NSCLC cells, and gene and protein levels were measured with qRT-PCR and Western blotting, respectively. NSCLC cell proliferation, migration and apoptosis were evaluated with CCK-8 assays, Ki-67 staining, Transwell assays and flow cytometry, respectively. Knocking down hsa_circ_0007580 inhibited proliferation and invasion by NSCLC cells and induced their apoptosis. Dual luciferase reporter assays indicated that miR-545-3p can bind to hsa_circ_0007580 (suggesting that hsa_circ_0007580 sponges miR-545-3p) and to protein kinase Ca (suggesting that miR-545-3p directly inhibits this gene). In a xenograft tumor model, downregulating hsa_circ_0007580 inhibited NSCLC tumorigenesis by inactivating p38/mitogen-activated protein kinase signaling. Thus, silencing hsa_circ_0007580 notably inhibited NSCLC progression in vitro and in vivo, suggesting this circRNA could be a novel treatment target for NSCLC.

Keywords: NSCLC; PRKCA; hsa_circ_0007580; miR-545-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Down-Regulation
  • Gene Knockdown Techniques
  • Humans
  • Lung Neoplasms / genetics*
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • RNA, Circular / genetics*
  • RNA, Neoplasm / genetics*
  • RNA, Small Interfering / genetics
  • Signal Transduction / genetics
  • Xenograft Model Antitumor Assays

Substances

  • MIR545 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA, Neoplasm
  • RNA, Small Interfering