Long non-coding RNA ZEB1-AS1 promotes colon adenocarcinoma malignant progression via miR-455-3p/PAK2 axis

Cell Prolif. 2020 Jan;53(1):e12723. doi: 10.1111/cpr.12723. Epub 2019 Dec 12.

Abstract

Objective: The long non-coding RNA zinc finger E-box-binding homeobox 1 antisense 1 (ZEB1-AS1) acts as an oncogenic regulator in many human tumours. In the present study, we identify the role and potential molecular biological mechanisms of ZEB1-AS1 in colon adenocarcinoma (COAD).

Methods: QRT-PCR was used to detect the expression of ZEB1-AS1, miR-455-3p and p21-activated kinases 2 (PAK2) in COAD tissues. CCK8 assay, EdU assay, transwell assay and scratch wound assay were used to explore the biological function of ZEB1-AS1 in COAD cells. Bioinformatics, luciferase reporter assays and an RNA pull-down assay were used to demonstrate the mechanism of ZEB1-AS1. We further explore the role of ZEB1-AS1 in vivo though xenograft tumour assay.

Results: We found that ZEB1-AS1 expression was significantly up-regulated in COAD tissues, and high ZEB1-AS1 level was correlated with the poor prognosis of COAD patients. MiR-455-3p plays an anti-cancer role in COAD by targeting PAK2. We confirmed that ZEB1-AS1 promotes PAK2 expression by sponging miR-455-3p, thus facilitating COAD cell growth and metastasis.

Conclusions: To sum up, this result illustrates the novel molecular mechanism of ZEB1-AS1 in COAD and provides a new target for the diagnosis and treatment of COAD patients.

Keywords: COAD; PAK2; ZEB1-AS1; growth and metastasis; miR-455-3p.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Animals
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Male
  • Mice
  • MicroRNAs / biosynthesis*
  • Neoplasm Metastasis
  • Neoplasm Proteins / metabolism*
  • RNA, Long Noncoding / biosynthesis*
  • RNA, Neoplasm / biosynthesis*
  • Signal Transduction*
  • Up-Regulation
  • p21-Activated Kinases / metabolism*

Substances

  • MIRN455 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Long Noncoding
  • RNA, Neoplasm
  • long non-coding RNA ZEB1-AS1, human
  • PAK2 protein, human
  • p21-Activated Kinases