lncRNA AFAP1-AS1 Promotes Migration and Invasion of Non-Small Cell Lung Cancer via Up-Regulating IRF7 and the RIG-I-Like Receptor Signaling Pathway

Cell Physiol Biochem. 2018;50(1):179-195. doi: 10.1159/000493967. Epub 2018 Oct 2.

Abstract

Background/aims: Accumulating evidence has highlighted the importance of long non-coding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) in tumor biology. Among others, actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) has been associated with non-small cell lung cancer (NSCLC). However, it remains unclear how AFAP1-AS1 participates in the development and progression of NSCLC.

Methods: The peripheral blood samples were collected from patients with NSCLC. White blood cell subsets were classified and levels of interleukin (IL)-10, IL-12 and IFN-γ in serum were measured. We then identified its target gene of AFAP1-AS1 via bioinformatics methods. NSCLC cell line with the highest expression of AFAP1-AS1, i.e. H1975 was selected for in vitro experiments. A series of inhibitor, vector and siRNA were employed to validate the regulatory mechanisms of AFAP1-AS1 in the development and progression of NSCLC. Cell proliferation was detected by MTT assay and EdU staining. Cell migration and invasion, and cell cycle and apoptosis were measured by transwell assay and flow cytometry, respectively.

Results: A high expression of AFAP1-AS1 was identified in NSCLC, alongside with a reduced level of IL-12 and increased levels of IL-10 and interferon (IFN)-γ. Aberrant expressions of AFAP1-AS1 were associated with pathological grade, TNM staging and metastatic potential of NSCLC. AFAP1-AS1 could activate interferon regulatory factor (IRF)7, the retinoid-inducible protein (RIG)-I-like receptor signaling pathway and Bcl-2 in vitro. Over-expression of AFAP1-AS1 promoted NSCLC cell proliferation, invasion and migration while inhibiting cell apoptosis.

Conclusion: lncRNA AFAP1-AS1 promotes migration and invasion of non-small cell lung cancer via up-regulating IRF7 and the RIG-I-like receptor signaling pathway.

Keywords: AFAP1-AS1; IRF7; Non-small cell lung cancer; RIG-I-like receptor signaling pathway; lncRNA.

MeSH terms

  • Apoptosis
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • DEAD Box Protein 58 / genetics
  • DEAD Box Protein 58 / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interferon Regulatory Factor-7 / genetics
  • Interferon Regulatory Factor-7 / metabolism*
  • Interleukin-10 / blood
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-12 / blood
  • Interleukin-12 / genetics
  • Interleukin-12 / metabolism
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • RNA Interference
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism
  • Receptors, Immunologic
  • Signal Transduction / genetics
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • AFAP1-AS1 long noncoding RNA, human
  • IRF7 protein, human
  • Interferon Regulatory Factor-7
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Receptors, Immunologic
  • Interleukin-10
  • Interleukin-12
  • RIGI protein, human
  • DEAD Box Protein 58