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癌症来源的外泌体 miR-7641 促进乳腺癌的进展和转移。

Cancer-derived exosomal miR-7641 promotes breast cancer progression and metastasis.

机构信息

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

出版信息

Cell Commun Signal. 2021 Feb 22;19(1):20. doi: 10.1186/s12964-020-00700-z.

Abstract

BACKGROUND

Intercellular communication is crucial for breast cancer progression and metastasis. However, the role of cancer-derived exosomes and their crucial microRNA (miRNA) cargoes mediating intercellular communication requires further investigation.

METHODS

Cancer-derived exosomes were isolated using differential centrifugation and differentially expressed miRNAs were determined by microarrays and qRT-PCR analysis. Cell proliferation, wound-healing, Transwell invasion, and tumor xenograft assays were used for functional research. Plasma exosomal RNA was isolated to verify its role as a prognostic biomarker.

RESULTS

We found that the tumor-promoting capacity of the exosomes was positively related to their cells of origin. MiR-7641 was identified to be the most differentially expressed miRNA, both at endogenous and secretory levels in high-metastatic cancer cells. MiR-7641 could promote tumor cell progression and metastasis, and that these functions of miR-7641 could alter recipient cells via transportation of exosomes. Additionally, exosomal miR-7641 could promote tumor growth in vivo; and its levels were significantly elevated in the plasma of patients with distant metastasis. Bioinformatics analysis has suggested that miR-7641 is correlated with breast cancer survival, and several important cellular and biological processes are closely targeted by miR-7641.

CONCLUSION

The findings indicate miR-7641 to be an important component of the cancer exosomes in promoting tumor progression and metastasis via intercellular communication. Additionally, exosomal miR-7641 may serve as a promising non-invasive diagnostic biomarker and potential targetable candidate in breast cancer treatment. Video Abstract.

摘要

背景

细胞间通讯对于乳腺癌的进展和转移至关重要。然而,癌症来源的外泌体及其介导细胞间通讯的关键 microRNA(miRNA)货物的作用仍需进一步研究。

方法

使用差速离心分离癌细胞来源的外泌体,并通过微阵列和 qRT-PCR 分析确定差异表达的 miRNA。通过细胞增殖、划痕愈合、Transwell 侵袭和肿瘤异种移植实验进行功能研究。分离血浆外泌体 RNA 以验证其作为预后生物标志物的作用。

结果

我们发现外泌体的促肿瘤能力与其细胞来源呈正相关。miR-7641 被鉴定为最具差异表达的 miRNA,无论是在内源性还是高转移性癌细胞的分泌水平上。miR-7641 可促进肿瘤细胞的进展和转移,并且这些 miR-7641 的功能可以通过外泌体的运输改变受体细胞。此外,外泌体 miR-7641 可在体内促进肿瘤生长;并且其在远处转移患者的血浆中的水平显著升高。生物信息学分析表明,miR-7641 与乳腺癌的生存相关,并且 miR-7641 密切靶向几个重要的细胞和生物学过程。

结论

这些发现表明,miR-7641 是促进肿瘤进展和转移的癌症外泌体的重要组成部分,通过细胞间通讯。此外,外泌体 miR-7641 可能作为一种有前途的非侵入性诊断生物标志物和乳腺癌治疗的潜在靶向候选物。视频摘要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3043/7898766/27a052cd1b30/12964_2020_700_Fig1_HTML.jpg

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