Long non-coding RNA Down syndrome cell adhesion molecule-anti-sense 1 promotes gastric carcinoma cell proliferation and migration by regulating the miR-204/TPT1 axis

Hum Exp Toxicol. 2021 Dec;40(12_suppl):S187-S195. doi: 10.1177/09603271211036037. Epub 2021 Aug 9.

Abstract

Background: Several recent studies have suggested that the long non-coding RNA (lncRNA) DSCAM-AS1 (Down syndrome cell adhesion molecule - anti-sense 1) is aberrantly expressed in many malignancies. Purpose: In this study, we aimed to explore the the role of DSCAM-AS1 in gastric carcinoma. Research Design: Expression of DSCAM-AS1 mRNA, miR-204, and TPT1 (Tumor Protein, Translationally-Controlled 1) were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Proliferation and apoptosis of GC cells were determined using the CCK-8 cell counting assay and flow cytometry. The rate of cell migration and invasion was determined using a transwell assay. The relationships between DSCAM-AS1, miR-204, and TPT1 were predicted and confirmed using a dual-luciferase reporter assay. Expression of TPT1 protein was quantified by Western blot. Results: In this study, we found that DSCAM-AS1 was significantly overexpressed in GC tissues and cell lines. Functional experiments indicated that GC cells with DSCAM-AS1 silencing exhibited a dynamic reduction in proliferation and migration. We identified miR-204 as a target of DSCAM-AS1 and found that it targeted TPT1 in GC cells, which further led to decreased expression of miR-204 in GC tissues and cell lines. A rescue assay revealed that knocked-down DSCAM-AS1 hindered GC progression, which was reversed upon miR-204 downregulation or TPT1 overexpression. Conclusion: We conclude that DSCAM-AS1 is expressed as a tumor oncogene in GC progression, modulated via the miR-204/TPT1 axis. These findings indicate the potential of DSCAM-AS1 as a therapeutic target for GC prevention.

Keywords: Long non-coding RNA DSCAM-AS1; TPT1; gastric carcinoma; miR-204.

MeSH terms

  • Animals
  • Cell Adhesion / genetics*
  • Cell Adhesion Molecules / genetics*
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Down Syndrome / genetics*
  • Down Syndrome / pathology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / genetics*
  • Stomach Neoplasms / pathology*
  • Tumor Protein, Translationally-Controlled 1 / metabolism*

Substances

  • Cell Adhesion Molecules
  • DSCAML1 protein, human
  • MIRN204 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TPT1 protein, human
  • Tumor Protein, Translationally-Controlled 1