Long non-coding RNA CCAT1/miR-218/ZFX axis modulates the progression of laryngeal squamous cell cancer

Tumour Biol. 2017 Jun;39(6):1010428317699417. doi: 10.1177/1010428317699417.

Abstract

Long non-coding RNAs have been proved to be closely associated with different cancers. This study was designed to elucidate the function and mechanisms of colon cancer-associated transcript-1 in the progression of human laryngeal squamous cell cancer. Expressions of colon cancer-associated transcript-1, microRNA-218, and zinc finger protein, X-linked messenger RNA were measured using quantitative real-time polymerase chain reaction, and the expression level of zinc finger protein, X-linked protein was detected using western blot. Proliferation and invasion of laryngeal squamous cell cancer cell lines were detected by Cell Counting Kit-8 assay and Transwell invasion assay, respectively. Luciferase assay was used to confirm whether microRNA-218 is a target of colon cancer-associated transcript-1 and whether microRNA-218 directly binds to 3'-untranslated region of zinc finger protein, X-linked messenger RNA. Effect of colon cancer-associated transcript-1 on tumor growth was observed through xenograft mice models in vivo. The results showed that expressions of colon cancer-associated transcript-1 and zinc finger protein, X-linked were significantly higher while microRNA-218 expression was significantly lower in the laryngeal squamous cell cancer tissues than those in the adjacent normal tissues. MicroRNA-218 overexpression or zinc finger protein, X-linked silencing significantly suppressed proliferation and invasion of laryngeal squamous cell cancer cells. Moreover, knockdown of colon cancer-associated transcript-1 significantly inhibited proliferation and invasion of laryngeal squamous cell cancer cells, which were reversed by microRNA-218 downregulation or zinc finger protein, X-linked upregulation. Finally, colon cancer-associated transcript-1 silencing inhibited xenograft tumor growth of laryngeal squamous cell cancer in vivo. In conclusion, colon cancer-associated transcript-1 knockdown inhibits proliferation and invasion of laryngeal squamous cell cancer cells through enhancing zinc finger protein, X-linked by sponging microRNA-218, elucidating a novel colon cancer-associated transcript-1-microRNA-218-zinc finger protein, X-linked regulatory axis in laryngeal squamous cell cancer and providing a promising therapeutic target for laryngeal squamous cell cancer patients.

Keywords: Colon cancer–associated transcript-1; X-linked; invasion; microRNA-218; proliferation; zinc finger protein.

MeSH terms

  • 3' Untranslated Regions
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kruppel-Like Transcription Factors / biosynthesis*
  • Kruppel-Like Transcription Factors / genetics
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / pathology
  • Male
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Neoplasm Invasiveness / genetics
  • Neoplasms, Squamous Cell / genetics*
  • Neoplasms, Squamous Cell / pathology
  • RNA, Long Noncoding / biosynthesis*
  • RNA, Long Noncoding / genetics
  • Signal Transduction

Substances

  • 3' Untranslated Regions
  • CCAT1 long noncoding RNA, human
  • Kruppel-Like Transcription Factors
  • MIRN218 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • zinc finger protein, X-linked