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

• Published in: Journal of cellular and molecular medicine 2022-01, Vol.26 (2), p.475-490
• Main Authors: Yi, Bolong, Li, Hao, Cai, Heng, Lou, Xin, Yu, Mingjun, Li, Zhen
• Format: Article
• Language: English
• Subjects: Amino Acid Oxidoreductases - metabolism; Angiogenesis; Animals; Antibodies; Behavior; CD34 antigen; Cell Line, Tumor; Cell lines; Cell migration; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Colorectal cancer; Gene Expression Regulation, Neoplastic; Glioma; Glioma - genetics; Glioma - pathology; Glioma cells; Humans; Liver cancer; LOXL1‐AS1; Lung cancer; Matrix Metalloproteinase 14 - genetics; Matrix Metalloproteinase 14 - metabolism; Medical prognosis; Membranes; Metastasis; Mice; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Mimicry; miRNA; miR‐374b‐5p; MMP14; Nervous system; Non-coding RNA; Original; Proteins; RNA, Long Noncoding - genetics; RNA-Binding Proteins - metabolism; TIAR; Tumors; vasculogenic mimicry; Xenografts
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.17106

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.