Long non‑coding RNA ZEB1‑AS1 predicts a poor prognosis and promotes cancer progression through the miR‑200a/ZEB1 signaling pathway in intrahepatic cholangiocarcinoma

Int J Oncol. 2020 Jun;56(6):1455-1467. doi: 10.3892/ijo.2020.5023. Epub 2020 Mar 20.

Abstract

Emerging evidence suggests that long non‑coding RNAs (lncRNAs) play pivotal roles in cancer progression, including in intrahepatic cholangiocarcinoma (IHCC). The overexpression of lncRNA ZEB1 antisense 1 (ZEB1‑AS1) has been discovered in several types of cancer; however, the clinical significance and functional role of ZEB1‑AS1 in IHCC have not yet been determined. In the present study, ZEB1‑AS1 was found to be upregulated in IHCC cell lines and tissues. A high ZEB1‑AS1 expression was associated with clinical progression and a poor survival of patients with IHCC, and was identified as an independent risk factor for a poor prognosis. In addition, ZEB1‑AS1 promoted the proliferation and metastasis of IHCC cells both in vitro and in vivo. ZEB1‑AS1 was demonstrated to increase the expression of ZEB1 by sponging miR‑200a and to thereby accelerate epithelial‑mesenchymal transition (EMT). On the whole, the findings of the present study demonstrate that ZEB1‑AS1 promotes proliferation and metastasis in IHCC, and induces EMT through the miR‑200a/ZEB1 signaling pathway. ZEB1‑AS1 may thus be a promising prognostic biomarker and essential therapeutic target for IHCC.

Keywords: non-coding RNA; intrahepatic cholangiocarcinoma; progression; prognosis.

MeSH terms

  • Bile Duct Neoplasms / genetics
  • Bile Duct Neoplasms / metabolism
  • Bile Duct Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / metabolism
  • Cholangiocarcinoma / pathology*
  • Disease Progression
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Signal Transduction
  • Survival Analysis
  • Up-Regulation
  • Zinc Finger E-box-Binding Homeobox 1 / genetics*
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

  • MIRN200 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • long non-coding RNA ZEB1-AS1, human