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外泌体 miR-155-5p 来源于神经胶质瘤干细胞样细胞,通过靶向 ACOT12 促进间充质转化。

Exosomal miR-155-5p derived from glioma stem-like cells promotes mesenchymal transition via targeting ACOT12.

机构信息

Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 230001, Hefei, Anhui, People's Republic of China.

Anhui Key Laboratory of Brain Function and Diseases, 230001, Hefei, Anhui, People's Republic of China.

出版信息

Cell Death Dis. 2022 Aug 19;13(8):725. doi: 10.1038/s41419-022-05097-w.

Abstract

Tumor-associated exosomes play essential roles in intercellular communication and the foundation of cancer microenvironment in glioma. Many mRNAs, microRNAs (miRNAs) and proteins contained in tumor-associated exosomes can be transferred to recipient cells and contribute to the progression of tumor. Nevertheless, the cellular communication between malignant cells with different heterogeneities or characteristics and resultant tumor progression are still unclear in glioma. Here, we show that exosomes released from glioma stem-like cells (GSCs) contain a significant increasing level of miR-155-5p and could be horizontally transferred to surrounding glioma cells. High expression of miR-155-5p in plasma exosomes from patients was associated with glioma diagnosis and grading. Mechanically, we found that miR-155-5p markedly reduced the expression of acetyl-CoA thioesterase 12 (ACOT12), which played as a tumor suppressor in glioma. Furthermore, mesenchymal transition was significantly promoted in glioma cells treated with GSCs-derived exosomes. In conclusion, GSCs-derived exosomal miR-155-5p play a critical role in glioma progression and facilitating tumor aggressive growth by targeting ACOT12 and promoting mesenchymal transition. Exosomal miR-155-5p is also a potential predictive biomarker for glioma, which may provoke the development of novel diagnostic and therapeutic strategies against glioma.

摘要

肿瘤相关外泌体在细胞间通讯和胶质瘤肿瘤微环境的形成中起着至关重要的作用。肿瘤相关外泌体中包含的许多 mRNAs、microRNAs (miRNAs) 和蛋白质可以转移到受体细胞,并促进肿瘤的进展。然而,在胶质瘤中,恶性细胞之间具有不同异质性或特征的细胞通讯以及由此产生的肿瘤进展仍然不清楚。在这里,我们表明,源自神经胶质瘤干细胞(GSCs)的外泌体中含有显着增加水平的 miR-155-5p,并可以水平转移到周围的神经胶质瘤细胞。患者血浆外泌体中 miR-155-5p 的高表达与胶质瘤的诊断和分级有关。从机制上讲,我们发现 miR-155-5p 显着降低了乙酰辅酶 A 硫酯酶 12 (ACOT12) 的表达,ACOT12 在胶质瘤中作为肿瘤抑制因子发挥作用。此外,用 GSCs 衍生的外泌体处理的神经胶质瘤细胞中,间充质转化明显增强。总之,GSCs 衍生的外泌体 miR-155-5p 通过靶向 ACOT12 并促进间充质转化,在胶质瘤进展和促进肿瘤侵袭性生长中发挥关键作用。外泌体 miR-155-5p 也是胶质瘤的潜在预测生物标志物,可能会引发针对胶质瘤的新型诊断和治疗策略的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bfc/9391432/9c79b184002b/41419_2022_5097_Fig1_HTML.jpg

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