LncRNA HAGLROS promotes breast cancer evolution through miR-135b-3p/COL10A1 axis and exosome-mediated macrophage M2 polarization.

IF 8.1 1区生物学 Q1 CELL BIOLOGY

Cell Death & Disease Pub Date : 2024-08-28 DOI:10.1038/s41419-024-07020-x

Ziqi Meng, Rui Zhang, Xuwei Wu, Zhengri Piao, Meihua Zhang, Tiefeng Jin

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Abstract

Long non-coding RNAs (lncRNAs) play an important role in breast cancer progression, but the function of lncRNAs in regulating tumor-associated macrophages (TAMs) remains unclear. As carriers of lncRNAs, exosomes play an important role as mediators in the communication between cancer cells and the tumor microenvironment. In this study, we found that lncRNA HAGLROS was highly expressed in breast cancer tissues and plasma exosomes, and its high expression was related to the poor prognosis of breast cancer patients. Functionally, breast cancer cell-derived exosomal lncRNA HAGLROS promotes breast cancer cell proliferation, migration, epithelial-mesenchymal transition (EMT) process and angiogenesis by inducing TAM/M2 polarization. Mechanistically, lncRNA HAGLROS competitively binds to miR-135-3p to prevent the degradation of its target gene COL10A1. Collectively, these results indicated that the lncRNA HAGLROS/miR-135b-3p/COL10A1 axis promoted breast cancer progression, and revealed the interactive communication mechanism between breast cancer cells and TAMs, suggesting that lncRNA HAGLROS may be a potential biomarker and therapeutic target for breast cancer.

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LncRNA HAGLROS通过miR-135b-3p/COL10A1轴和外泌体介导的巨噬细胞M2极化促进乳腺癌进化。

长非编码RNA（lncRNA）在乳腺癌的进展中发挥着重要作用，但lncRNA在调控肿瘤相关巨噬细胞（TAMs）方面的功能仍不清楚。作为 lncRNAs 的载体，外泌体在癌细胞与肿瘤微环境的交流中发挥着重要的媒介作用。本研究发现，lncRNA HAGLROS在乳腺癌组织和血浆外泌体中高表达，其高表达与乳腺癌患者的不良预后有关。在功能上，乳腺癌细胞外泌体lncRNA HAGLROS通过诱导TAM/M2极化促进乳腺癌细胞增殖、迁移、上皮-间质转化（EMT）过程和血管生成。从机制上讲，lncRNA HAGLROS与miR-135-3p竞争性结合，阻止其靶基因COL10A1的降解。总之，这些结果表明，lncRNA HAGLROS/miR-135b-3p/COL10A1轴促进了乳腺癌的进展，并揭示了乳腺癌细胞与TAM之间的互动交流机制，提示lncRNA HAGLROS可能是乳腺癌的潜在生物标志物和治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Death & Disease CELL BIOLOGY-

CiteScore

15.10

自引率

2.20%

发文量

935

审稿时长

2 months

期刊介绍： Brought to readers by the editorial team of Cell Death & Differentiation, Cell Death & Disease is an online peer-reviewed journal specializing in translational cell death research. It covers a wide range of topics in experimental and internal medicine, including cancer, immunity, neuroscience, and now cancer metabolism. Cell Death & Disease seeks to encompass the breadth of translational implications of cell death, and topics of particular concentration will include, but are not limited to, the following: Experimental medicine Cancer Immunity Internal medicine Neuroscience Cancer metabolism

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