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IF 3.1 4区医学 Q2 PHARMACOLOGY & PHARMACY

Naunyn-Schmiedeberg's archives of pharmacology Pub Date : 2024-12-16 DOI:10.1007/s00210-024-03646-y

Shouren Chen, Songjie Tu, Yan Huang, Hong Lin, Yuzhe Wang, Xuejun Dai

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引用次数: 0

摘要

长非编码RNA（lncRNA）参与胶质瘤癌变的研究已逐渐被发现。本文旨在探讨lncRNA muskelin 1 antisense RNA（MKLN1-AS）在胶质瘤细胞致癌过程中的功能和机制。我们利用定量实时聚合酶链反应检测了MKLN1-AS、miR-126-5p和TEAD1（TEA结构域转录因子1）mRNA的表达。使用 5-乙炔基-2'-脱氧尿苷、流式细胞术、伤口愈合、transwell 和管形成试验分别鉴定了胶质瘤细胞的致癌特性。用 Western 印迹法检测了 TEAD1 蛋白、迁移相关蛋白和 Hippo 通路相关蛋白的水平。使用双荧光素酶报告和牵引实验证实了 miR-126-5p 与 MKLN1-AS 或 TEAD1 的结合。建立了小鼠异种移植模型进行体内分析。MKLN1-AS在胶质瘤组织和细胞系中的水平较高，在功能上，MKLN1-AS缺乏可抑制胶质瘤细胞的增殖、迁移、侵袭和血管生成，在体外可诱导细胞凋亡，在体内可阻碍肿瘤生长。从机制上看，MKLN1-AS靶向miR-126-5p，miR-126-5p直接靶向TEAD1。MKLN1-AS缺乏对胶质瘤细胞致癌特性的抑制作用被TEAD1过表达或miR-126-5p抑制所取消。此外，MKLN1-AS/miR-126-5p介导了TEAD1对Hippo通路的激活。通过miR-126-5p，MKLN1-AS通过TEAD1-Hippo通路削弱胶质瘤细胞的致癌表型和生长，为胶质瘤分子治疗提供了新的治疗靶点。

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LncRNA MKLN1-AS promotes glioma tumorigenesis and growth via activating the Hippo pathway through miR-126-5p/TEAD1 axis.

The involvement of long non-coding RNAs (lncRNAs) in glioma carcinogenesis has gradually been identified. Herein, we aimed to explore the function and mechanism of lncRNA muskelin 1 antisense RNA (MKLN1-AS) in glioma cell oncogenic properties. Quantitative real-time polymerase chain reaction was utilized to test the expression of MKLN1-AS, miR-126-5p, and TEAD1 (TEA Domain Transcription Factor 1) mRNA expression. Oncogenic properties of glioma cells were characterized using 5-ethynyl-2'-deoxyuridine, flow cytometry, wound healing, transwell, and tube formation assays, respectively. Levels of TEAD1 protein, mobility-related proteins, and Hippo pathway-related proteins were examined by Western blotting. The binding between miR-126-5p and MKLN1-AS or TEAD1 was confirmed by using dual-luciferase reporter and pull-down assays. The murine xenograft model was established for in vivo analysis. Levels of MKLN1-AS in glioma tissues and cell lines were higher, functionally, MKLN1-AS deficiency could suppress glioma cell proliferation, migration, invasion, and angiogenesis, and induce apoptosis in vitro, as well as impede tumor growth in vivo. Mechanistically, miR-126-5p was targeted by MKLN1-AS, miR-126-5p directly targeted TEAD1. The suppressing effects of MKLN1-AS deficiency on glioma cell oncogenic properties were abolished by TEAD1 overexpression or miR-126-5p inhibition. Besides, MKLN1-AS/miR-126-5p mediates the activation of Hippo pathway by TEAD1. MKLN1-AS knockdown weakened glioma cell oncogenic phenotypes and growth via TEAD1-Hippo pathway through miR-126-5p, indicating a new therapeutic target for glioma molecular therapy.

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来源期刊

Naunyn-Schmiedeberg's archives of pharmacology 医学-药学

CiteScore

6.20

自引率

5.60%

发文量

142

审稿时长

4-8 weeks

期刊介绍： Naunyn-Schmiedeberg''s Archives of Pharmacology was founded in 1873 by B. Naunyn, O. Schmiedeberg and E. Klebs as Archiv für experimentelle Pathologie und Pharmakologie, is the offical journal of the German Society of Experimental and Clinical Pharmacology and Toxicology (Deutsche Gesellschaft für experimentelle und klinische Pharmakologie und Toxikologie, DGPT) and the Sphingolipid Club. The journal publishes invited reviews, original articles, short communications and meeting reports and appears monthly. Naunyn-Schmiedeberg''s Archives of Pharmacology welcomes manuscripts for consideration of publication that report new and significant information on drug action and toxicity of chemical compounds. Thus, its scope covers all fields of experimental and clinical pharmacology as well as toxicology and includes studies in the fields of neuropharmacology and cardiovascular pharmacology as well as those describing drug actions at the cellular, biochemical and molecular levels. Moreover, submission of clinical trials with healthy volunteers or patients is encouraged. Short communications provide a means for rapid publication of significant findings of current interest that represent a conceptual advance in the field.