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长链非编码 RNA HAGLROS 通过 miR-135b-3p/COL10A1 轴和外泌体介导的巨噬细胞 M2 极化促进乳腺癌的演进。

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

机构信息

Department of Central Laboratory, Yanbian University Hospital, Yanji, China.

Department of Pathology and Cancer Research Center, Yanbian University, Yanji, China.

出版信息

Cell Death Dis. 2024 Aug 28;15(8):633. doi: 10.1038/s41419-024-07020-x.

DOI:10.1038/s41419-024-07020-x
PMID:39198393
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11358487/
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.

摘要

长链非编码 RNA（lncRNA）在乳腺癌的进展中起着重要作用，但 lncRNA 调节肿瘤相关巨噬细胞（TAMs）的功能仍不清楚。作为 lncRNA 的载体，外泌体作为癌症细胞与肿瘤微环境之间通讯的介质发挥着重要作用。在本研究中，我们发现 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相关。功能上，乳腺癌细胞来源的外泌体 lncRNA HAGLROS 通过诱导 TAM/M2 极化促进乳腺癌细胞增殖、迁移、上皮-间充质转化（EMT）过程和血管生成。机制上，lncRNA HAGLROS 竞争性结合 miR-135-3p 以防止其靶基因 COL10A1 的降解。综上所述，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 TAMs 之间的交互通讯机制，表明 lncRNA HAGLROS 可能是乳腺癌的潜在生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a1/11358487/b1a39f3f0b4b/41419_2024_7020_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a1/11358487/d9d8f47735c5/41419_2024_7020_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a1/11358487/5256a90f4216/41419_2024_7020_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a1/11358487/9e2aa575a619/41419_2024_7020_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a1/11358487/51df05df5aaf/41419_2024_7020_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a1/11358487/cdeab23e1ef5/41419_2024_7020_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a1/11358487/807cc8446459/41419_2024_7020_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a1/11358487/65204765b3a2/41419_2024_7020_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a1/11358487/b1a39f3f0b4b/41419_2024_7020_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a1/11358487/d9d8f47735c5/41419_2024_7020_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a1/11358487/5256a90f4216/41419_2024_7020_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a1/11358487/9e2aa575a619/41419_2024_7020_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a1/11358487/51df05df5aaf/41419_2024_7020_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a1/11358487/cdeab23e1ef5/41419_2024_7020_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a1/11358487/807cc8446459/41419_2024_7020_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a1/11358487/65204765b3a2/41419_2024_7020_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8a1/11358487/b1a39f3f0b4b/41419_2024_7020_Fig8_HTML.jpg

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