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LINC01278 通过抑制 mTOR 信号通路诱导自噬来抑制肿瘤进展。

LINC01278 Induces Autophagy to Inhibit Tumour Progression by Suppressing the mTOR Signalling Pathway.

机构信息

State Key Laboratory of Ophthalmology, Optometry, And Vision Science, Wenzhou Medical University, Wenzhou, China.

The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, China.

出版信息

Oxid Med Cell Longev. 2023 Jan 18;2023:8994901. doi: 10.1155/2023/8994901. eCollection 2023.

Abstract

Uveal melanoma (UM) is an aggressive intraocular malignant tumour that is closely related to autophagic dysfunction. We aimed to identify autophagy-related long noncoding RNAs (lncRNAs) to elucidate the molecular mechanism of UM. Here, we show that LINC01278 is a new potential biomarker with clinical prognostic value in UM through bioinformatics analysis. Application of an autophagy inhibitor (3-MA) and an autophagy agonist (MG-132) indicated that LINC01278 can inhibit UM cell proliferation, migration, and invasion by inducing autophagy. A xenograft nude mouse model was used to examine the tumorigenesis of UM cells in vivo. Mechanistically, LINC01278 can inhibit the mTOR signalling pathway to activate autophagy, as shown by experiments with an mTOR agonist (MHY1485) and mTOR inhibitor (rapamycin) treatment. Our findings indicate that LINC01278 functions as a tumour suppressor by inhibiting the mTOR signalling pathway to induce autophagy. Targeting the LINC01278-mTOR axis might be a novel and promising therapeutic approach for UM.

摘要

葡萄膜黑色素瘤 (UM) 是一种侵袭性眼内恶性肿瘤,与自噬功能障碍密切相关。我们旨在鉴定与自噬相关的长链非编码 RNA (lncRNA),以阐明 UM 的分子机制。在这里,我们通过生物信息学分析表明,LINC01278 是一种新的潜在生物标志物,具有 UM 的临床预后价值。自噬抑制剂 (3-MA) 和自噬激动剂 (MG-132) 的应用表明,LINC01278 可以通过诱导自噬来抑制 UM 细胞的增殖、迁移和侵袭。裸鼠异种移植模型用于体内研究 UM 细胞的致瘤性。机制上,LINC01278 可以抑制 mTOR 信号通路来激活自噬,这可以通过使用 mTOR 激动剂 (MHY1485) 和 mTOR 抑制剂 (雷帕霉素) 处理来证明。我们的研究结果表明,LINC01278 通过抑制 mTOR 信号通路诱导自噬来发挥肿瘤抑制作用。靶向 LINC01278-mTOR 轴可能是治疗 UM 的一种新的有前途的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b4e/9876672/53d898cef9cf/OMCL2023-8994901.001.jpg

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