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长链非编码RNA MALAT1通过调控骨肉瘤中的微小RNA-150-5p/血管内皮生长因子A信号促进肿瘤血管生成: 及分析

LncRNA MALAT1 Promotes Tumor Angiogenesis by Regulating MicroRNA-150-5p/VEGFA Signaling in Osteosarcoma: and Analyses.

作者信息

Vimalraj Selvaraj, Subramanian Raghunandhakumar, Dhanasekaran Anuradha

机构信息

Centre for Biotechnology, Anna University, Chennai, India.

Department of Pharmacology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, India.

出版信息

Front Oncol. 2021 Oct 7;11:742789. doi: 10.3389/fonc.2021.742789. eCollection 2021.

Abstract

The present study aims to analyze the expression of long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in human osteosarcoma (OS) cells and to investigate its role in OS-induced angiogenesis. MALAT1 expression in OS cells was significantly higher than in normal osteoblasts. The functional analysis indicated that MALAT1 appears to enhance OS-induced angiogenesis, and analyses, endothelial cell proliferation and migration, chick embryo angiogenesis assay, and zebrafish xenograft model. Mechanistically, silencing MALAT1 downregulated vascular endothelial growth factor A (VEGFA) expression and upregulated miR-150-5p expression in OS cells, and MALAT1-mediated angiogenic induction by VEGFA in OS microenvironment. Moreover, MALAT1 directly targeted miR-150-5p and miR-150-5p directly target VEGFA in OS. Overexpression of miR-150-5p downregulates VEGFA expression in OS. More notably, we showed that MALAT1 induced angiogenesis in OS microenvironment by upregulating the expression of VEGFA targeting miR-150-5p. Overall, our findings suggest that MALAT1 promotes angiogenesis by regulating the miR-150-5p/VEGFA signaling in OS microenvironment. The findings of the molecular mechanisms of MALAT1 in tumor angiogenesis offer a new viewpoint on OS treatment.

摘要

本研究旨在分析长链非编码RNA(lncRNA)转移相关肺腺癌转录本1(MALAT1)在人骨肉瘤(OS)细胞中的表达,并探讨其在骨肉瘤诱导血管生成中的作用。骨肉瘤细胞中MALAT1的表达显著高于正常成骨细胞。功能分析表明,MALAT1似乎增强了骨肉瘤诱导的血管生成,并通过内皮细胞增殖和迁移分析、鸡胚血管生成分析和斑马鱼异种移植模型进行了研究。机制上,沉默MALAT1可下调骨肉瘤细胞中血管内皮生长因子A(VEGFA)的表达并上调miR-150-5p的表达,且MALAT1在骨肉瘤微环境中通过VEGFA介导血管生成诱导。此外,MALAT1直接靶向miR-150-5p,而miR-150-5p在骨肉瘤中直接靶向VEGFA。miR-150-5p的过表达可下调骨肉瘤中VEGFA的表达。更值得注意的是,我们发现MALAT1通过上调靶向miR-150-5p的VEGFA的表达在骨肉瘤微环境中诱导血管生成。总体而言,我们的研究结果表明,MALAT1通过调节骨肉瘤微环境中的miR-150-5p/VEGFA信号促进血管生成。MALAT1在肿瘤血管生成中的分子机制研究结果为骨肉瘤治疗提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1866/8529043/2915f321aed2/fonc-11-742789-g001.jpg

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