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

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.

T-Cell Intracellular Antigen 1-Like Protein in Physiology and Pathology

“…Some relevant examples include iNOS [ 70 ], TPD52 [ 71 ] and alpha-synuclein [ 60 ] mRNAs. Stability/turnover events can involve RNAs and SGs [ 72 ], and also non-coding RNAs (lncRNAs/miRNAs) [ 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 ]. An example of this is the Hippo pathway, which is a regulator of organ growth and tumorigenesis.…”

“…For example, the lncRNA MT1JP functions as a tumor suppressor by interacting with TIAR to modulate p53 signaling [ 74 ]. Similarly, the lncRNA PHAROH regulates Myc translation in hepatocellular carcinoma by sequestering TIAL1 [ 75 ], and the lncRNA LOXL1-AS1 interacts with TIAR to modulate vasculogenic mimicry in glioma through the regulation of the miR-374b-5p/MMP14 axis [ 76 ]. Interestingly, several single nucleotide polymorphisms in lncRNA regions found in TIAR are associated with breast cancer risk [ 77 ].…”

“…Interestingly, several single nucleotide polymorphisms in lncRNA regions found in TIAR are associated with breast cancer risk [ 77 ]. The participation of miRNAs has also been reported—for example, the interaction between miR-223-3p and TIAL1, which downregulates TIAL1, is involved in the neuroprotective effects of dexmedetomidine on hippocampal neuronal cells in vitro [ 78 ], as well as vasculogenic mimicry in glioma via the regulation of the miR-374b-5p/MMP14 axis [ 76 ]. As stated earlier, TIAR/Rox8 promotes miRNA-dependent yki messenger RNA decay [ 73 ].…”

“…As already mentioned, TIAR interacts with LOXL1-AS1 to modulate vasculogenic mimicry in glioma via the miR-374b-5p/MMP14 axis. This observation might reveal novel targets for glioma therapy [ 76 ].…”

Immunotherapeutic Targeting of NG2/CSPG4 in Solid Organ Cancers

“…NG2/CSPG4 is a malignant marker in CNS cancers such as gliomas, the most common and malignant cancer in the CNS [ 28 ], and it is closely related to poor prognoses as it promotes cancer cell proliferation and motility via its binding to growth factors (bFGF and PDGF-AA) [ 24 ], MMPs [ 29 ], ECM-collagen IV [ 30 ], and integrins [ 31 ], which involves these binding partners in an oncogenic transformation. There is an inverse relationship between the activation of á3â1 integrin-dependent PI3K/Akt signaling promoted by NG2/CSPG4 and apoptosis, as demonstrated by the restoration of apoptosis after siRNA knockdown of NG2/CSPG4 [ 32 ].…”