Circ_0067934 promotes non-small cell lung cancer development by regulating miR-1182/KLF8 axis and activating Wnt/β-catenin pathway

Biomed Pharmacother. 2020 Sep:129:110461. doi: 10.1016/j.biopha.2020.110461. Epub 2020 Jul 16.

Abstract

Non-small cell lung cancer (NSCLC) is the primary subtype of lung cancer with high mortality. Circular RNAs (circRNAs) play a crucial role in tumor development and progression. This study aimed to explore the function of circ_0067934 in NSCLC progression and its molecular basis. The levels of circ_0067934, miR-1182 and kruppel like factor 8 (KLF8) were measured by quantitative real-time polymerase chain reaction or western blot assay. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay. Cell migration and invasion were assessed by transwell assay. Cell apoptosis was monitored by flow cytometry. The protein levels of epithelial-to-mesenchymal transition (EMT)-related markers and Wnt/β-catenin pathway-related proteins were examined by western blot. Dual-luciferase reporter assay, RNA Immunoprecipitation (RIP) assay or RNA pull-down assay was performed to verify the interaction among circ_0067934, miR-1182 and KLF8. Xenograft assay was used to detect tumor growth in vivo. We found that circ_0067934 and KLF8 were up-regulated, while miR-1182 was down-regulated in NSCLC tissues and cells. Circ_0067934 knockdown blocked proliferation, migration, invasion and EMT and induced apoptosis in NSCLC cells. Circ_0067934 regulated NSCLC progression by sponging miR-1182. MiR-1182 targeted KLF8 to hinder NSCLC development. In addition, depletion of circ_0067934 restrained tumor growth in vivo. In conclusion, Circ_0067934 acted as a competing endogenous RNA to facilitate NSCLC progression by regulating the miR-1182/KLF8 axis and activating Wnt/β-catenin pathway.

Keywords: Circ_0067934; KLF8; Non-small cell lung cancer; Wnt/β-catenin pathway; miR-1182.

MeSH terms

  • Animals
  • Apoptosis
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Tumor Burden
  • Wnt Signaling Pathway*

Substances

  • KLF8 protein, human
  • Kruppel-Like Transcription Factors
  • MIRN1182 microRNA, human
  • MicroRNAs
  • RNA, Circular