LOXL1-AS1 communicating with TIAR modulates vasculogenic mimicry in glioma via regulation of the miR-374b-5p/MMP14 axis

J Cell Mol Med. 2022 Jan;26(2):475-490. doi: 10.1111/jcmm.17106. Epub 2021 Dec 8.

Abstract

At present, growing evidence indicates that long non-coding RNAs (lncRNAs) participate in the progression of glioma. The function of LOXL1-AS1 in vasculogenic mimicry (VM) in glioma remains unclear. First, the expressions of TIAR, the lncRNA LOXL1-AS1, miR-374b-5p and MMP14 were examined by qRT-PCR and Western blot in both, glioma tissues and glioma cell lines. Proliferation, migration, invasion and tube formation assays were conducted to evaluate the roles of TIAR, LOXL1-AS1, miR-374b-5p and MMP14 in malignant cellular behaviours in glioma cells. A nude mouse xenograft model and dual staining for CD34 and PAS were used to assess whether VM was affected by TIAR, LOXL1-AS1 or miR-374b-5p in vivo. In this study, low levels of TIAR and high levels of LOXL1-AS1 were found in glioma cells and tissues. TIAR downregulated the expression of LOXL1-AS1 by destabilizing it. LOXL1-AS1 acted like a miRNA sponge towards miR-374b-5p so that downregulation of the former greatly inhibited cell proliferation, migration, invasion and VM. Additionally, miR-374b-5p overexpression repressed malignant biological behaviours and VM in glioma by modifying MMP14. In summary, we demonstrated that TIAR combined with LOXL1-AS1 modulates VM in glioma via the miR-374b-5p/MMP14 axis, revealing novel targets for glioma therapy.

Keywords: LOXL1-AS1; miR-374b-5p; MMP14; TIAR; glioma; vasculogenic mimicry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / metabolism
  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Glioma* / genetics
  • Glioma* / pathology
  • Humans
  • Matrix Metalloproteinase 14 / genetics
  • Matrix Metalloproteinase 14 / metabolism
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA-Binding Proteins / metabolism

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • TIAL1 protein, human
  • Amino Acid Oxidoreductases
  • LOXL1 protein, human
  • MMP14 protein, human
  • Matrix Metalloproteinase 14