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LOXL1-AS1 通过调节 miR-374b-5p/MMP14 轴与 TIAR 通讯调节胶质瘤中的血管生成拟态。

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

机构信息

Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China.

Liaoning Clinical Medical Research Center in Nervous System Disease, Shenyang, China.

出版信息

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.

摘要

目前,越来越多的证据表明长非编码 RNA(lncRNA)参与了胶质瘤的进展。LOXL1-AS1 在胶质瘤中的血管生成拟态(VM)中的功能尚不清楚。首先,通过 qRT-PCR 和 Western blot 检测了胶质瘤组织和胶质瘤细胞系中 TIAR、lncRNA LOXL1-AS1、miR-374b-5p 和 MMP14 的表达。通过增殖、迁移、侵袭和管形成实验评估了 TIAR、LOXL1-AS1、miR-374b-5p 和 MMP14 在胶质瘤细胞恶性细胞行为中的作用。裸鼠异种移植模型和 CD34 和 PAS 双重染色用于评估 TIAR、LOXL1-AS1 或 miR-374b-5p 在体内对 VM 的影响。在本研究中,发现 TIAR 水平低,LOXL1-AS1 水平高在胶质瘤细胞和组织中。TIAR 通过使其不稳定而下调 LOXL1-AS1 的表达。LOXL1-AS1 充当 miR-374b-5p 的 miRNA 海绵,因此前者的下调极大地抑制了细胞增殖、迁移、侵袭和 VM。此外,miR-374b-5p 的过表达通过修饰 MMP14 抑制了胶质瘤中恶性生物学行为和 VM。总之,我们证明 TIAR 与 LOXL1-AS1 通过 miR-374b-5p/MMP14 轴调节胶质瘤中的 VM,为胶质瘤治疗提供了新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b032/8743654/eabc3e3da76f/JCMM-26-475-g006.jpg

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