Long non-coding RNA ZFAS1 regulates the malignant progression of gastric cancer via the microRNA-200b-3p/Wnt1 axis

Biosci Biotechnol Biochem. 2019 Jul;83(7):1289-1299. doi: 10.1080/09168451.2019.1606697. Epub 2019 Apr 18.

Abstract

Gastric cancer is a common malignant tumor. Studies from our laboratory or others have shown that long non-coding RNA (lncRNA) zinc finger antisense (ZFAS)1 often acts as an oncogene. However, the molecular underpinnings of how ZFAS1 regulates gastric cancer remain to be elucidated. Results showed that ZFAS1 expression was upregulated, and microRNA-200b-3p (miR-200b) expression was downregulated in gastric cancer tissues. MiR-200b overexpression suppressed the proliferation, cell cycle process, and Wnt/β-catenin signaling of gastric cancer cells. Subsequently, we identified miR-200b is a target of ZFAS1 and Wnt1 is a target of miR-200b. Furthermore, promotion of cancer malignant progression and activation of Wnt/β-catenin signaling induced by ZFAS1 was counteracted by increasing miR-200b expression. In vivo, ZFAS1 knockdown suppressed the tumorigenesis with the upregulated miR-200b and the inactive Wnt/β-catenin signaling. Summarily, we demonstrated a critical role of miR-200b in gastric cancer, and ZFAS1 can promote malignant progression through regulating miR-200b mediated Wnt/β-catenin signaling.

Keywords: Long non-coding RNA zinc finger antisense 1; Wnt/β-catenin signaling; gastric cancer; malignant progression; microRNA-200b-3p.

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Gene Knockdown Techniques
  • Heterografts
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / physiology*
  • Signal Transduction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology*
  • Tumor Cells, Cultured
  • Wnt1 Protein / metabolism*
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, human
  • MIRN200 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • WNT1 protein, human
  • Wnt1 Protein
  • ZFAS1 long non-coding RNA, human
  • beta Catenin