Long non-coding ribonucleic acid zinc finger antisense 1 promotes the progression of colonic cancer by modulating ZEB1 expression

J Gastroenterol Hepatol. 2017 Jun;32(6):1204-1211. doi: 10.1111/jgh.13646.

Abstract

Background and aim: Long non-coding RNA zinc finger antisense 1 (ZFAS1) is frequently amplified in hepatocellular carcinoma and promotes metastasis by increasing zinc finger E-box binding homeobox 1 (ZEB1), which can potentiate the progression of epithelial-to-mesenchymal transition (EMT). However, the expression pattern and role of ZFAS1 in colonic cancer remains unknown. The present study aimed to investigate the role of ZFAS1 and its clinical significance in colonic cancer.

Methods: Paired clinical colonic cancer tissue samples and clinicopathologic characteristics of 73 patients were analyzed. Quantitative real-time polymerase chain reaction analysis was used to evaluate expression levels of ZFAS1 in colonic cancer tissues, cell lines, and plasma. ZEB1 and EMT-related markers expression levels also were explored. Cell biology assays were used to explore the biologic consequences of ZFAS1 in regulating cell proliferation and invasion, as well as the roles in regulating EMT.

Results: Zinc finger antisense 1 was up-regulated in colonic cancer tissues compared with adjacent mucosa (P < 0.01), and its expression level was significantly correlated with TNM stage, vascular invasion, and lymph node metastasis (P < 0.05). ZFAS1 and ZEB1 were also increased in patients' plasma. Moreover, ZFAS1 promoted proliferation, invasion, and impeded apoptosis. Knockdown of ZFAS1 decreased expression of ZEB1 and increased the epithelial markers E-cadherin, ZO-1 while decreasing mesenchymal markers vimentin and N-cadherin.

Conclusions: Long non-coding RNA ZFAS1 may function as an oncogene by modulating ZEB1 to induce EMT. Manipulation of ZFAS1 level may be a novel approach to suppress colonic cancer progression. In addition, ZFAS1 in plasma has the potential to be a diagnostic biomarker of colonic cancer.

Keywords: EMT; LncRNA ZFAS1; ZEB1; colonic cancer.

MeSH terms

  • Biomarkers / blood
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colonic Neoplasms / diagnosis
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology*
  • Disease Progression
  • Epithelial-Mesenchymal Transition
  • Gene Expression / genetics*
  • Humans
  • Lymphatic Metastasis
  • Neoplasm Invasiveness / genetics
  • Neoplasm Staging
  • RNA, Long Noncoding / physiology*
  • Real-Time Polymerase Chain Reaction
  • Up-Regulation
  • Zinc Finger E-box-Binding Homeobox 1 / blood
  • Zinc Finger E-box-Binding Homeobox 1 / genetics*
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism*
  • Zinc Finger E-box-Binding Homeobox 1 / physiology

Substances

  • Biomarkers
  • Cadherins
  • RNA, Long Noncoding
  • ZEB1 protein, human
  • ZFAS1 long non-coding RNA, human
  • Zinc Finger E-box-Binding Homeobox 1