Circular RNA circTTBK2 facilitates non-small-cell lung cancer malignancy through the miR-873-5p/TEAD1/DERL1 axis

Epigenomics. 2022 Aug;14(16):931-949. doi: 10.2217/epi-2021-0480. Epub 2022 Aug 2.

Abstract

Aim: The underlying mechanisms by which circular RNAs (circRNAs) regulate non-small-cell lung cancer (NSCLC) progression remain elusive. This study investigated the role of circRNA circTTBK2 in NSCLC tumorigenesis. Materials & methods: Quantitative reverse transcriptase polymerase chain reaction analysis of circTTBK2 in NSCLC tissues and cell lines was performed. Cell proliferation, migration, invasion and tumorigenesis were confirmed in vitro and in vivo using CCK-8, EdU incorporation, Transwell assays and xenograft technique. The circTTBK2/miR-873-5p/TEAD1/DERL1 axis was verified by RNA immunoprecipitation, chromatin immunoprecipitation and luciferase reporter assays. Results: Overexpressed circTTBK2 in NSCLC tissues indicates poor prognosis of NSCLC patients. circTTBK2 harbors miR-873-5p, and miR-873-5p directly targets TEAD1. TEAD1 transcriptionally activates DERL1. Conclusion: This study revealed a novel machinery of circTTBK2/miR-873-5p/TEAD1/DERL1 for NSCLC tumorigenesis.

Keywords: DERL1; NSCLC; TEAD1; circTTBK2; miR-873-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Carcinogenesis / genetics
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Membrane Proteins / genetics
  • MicroRNAs* / genetics
  • Nuclear Proteins / genetics
  • RNA, Circular* / genetics
  • TEA Domain Transcription Factors / genetics

Substances

  • DERL1 protein, human
  • DNA-Binding Proteins
  • MIRN873 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Circular
  • TEA Domain Transcription Factors
  • TEAD1 protein, human