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外泌体 miR-183-5p 通过调控 FOXO1 促进结直肠癌血管生成。

Exosomal miR-183-5p promotes angiogenesis in colorectal cancer by regulation of FOXO1.

机构信息

Department of Laboratory Medicine, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, P.R. China.

Department of Pharmacy, Putuo People's Hospital, Shanghai, P.R. China.

出版信息

Aging (Albany NY). 2020 May 3;12(9):8352-8371. doi: 10.18632/aging.103145.

Abstract

Exosomes play important roles in proliferation and microenvironment modulation of many types of cancers, including colorectal cancer (CRC). However, the inhibitory effect of CRC cells-derived exosomes in angiogenesis has not been fully discussed. In this study, the roles of microRNA-183-5p (miR-183-5p) in abundant in exosomes secreted from the CRC cells were investigated. Initially, microarray analysis was employed to determine the differentially expressed miRNAs. Exosomes isolated from CRC cells were co-cultured with HMEC-1 cells to explore the role of exosomes in angiogenesis. Further, the effects of CRC cell-derived exosomal miR-183-5p on proliferation, invasion and tube formation abilities of HMEC-1 cells were assessed. The preventative effect of exosomal miR-183-5p was measured in nude mice. Initially, it was found that FOXO1 was downregulated while miR-183-5p was upregulated in CRC. Additionally, the inhibition of miR-183-5p was suggested to suppress proliferation, invasion and tube formation abilities of HMEC-1 cells through upregulating FOXO1. Then, assays demonstrated that CRC cell-derived exosomes overexpressing miR-183-5p contributed to an enhanced proliferation, invasion and tube formation abilities of HMEC-1 cells. Furthermore, experiments confirmed the tumor-promotive effects of CRC cell-derived exosomal miR-183-5p. Collectively, our study demonstrates that the CRC cell-derived exosomes overexpressing miR-183-5p aggravates CRC through the regulation of FOXO1. Exosomes overexpressing miR-183-5p might be a potential treatment biomarker for CRC.

摘要

外泌体在许多类型的癌症(包括结直肠癌(CRC))的增殖和微环境调节中发挥重要作用。然而,CRC 细胞来源的外泌体在血管生成中的抑制作用尚未得到充分讨论。在这项研究中,研究了 CRC 细胞来源的外泌体中丰富的 microRNA-183-5p(miR-183-5p)的作用。最初,使用微阵列分析确定差异表达的 miRNAs。将从 CRC 细胞分离的外泌体与 HMEC-1 细胞共培养,以研究外泌体在血管生成中的作用。此外,评估了 CRC 细胞衍生的外泌体 miR-183-5p 对 HMEC-1 细胞增殖、侵袭和管形成能力的影响。在裸鼠中测量了外泌体 miR-183-5p 的预防作用。最初发现 FOXO1 在 CRC 中下调,而 miR-183-5p 上调。此外,抑制 miR-183-5p 被认为通过上调 FOXO1 来抑制 HMEC-1 细胞的增殖、侵袭和管形成能力。然后,实验表明 CRC 细胞来源的过表达 miR-183-5p 的外泌体有助于增强 HMEC-1 细胞的增殖、侵袭和管形成能力。此外,实验证实了 CRC 细胞来源的外泌体 miR-183-5p 的促肿瘤作用。总之,我们的研究表明,过表达 miR-183-5p 的 CRC 细胞衍生的外泌体通过调节 FOXO1 加重 CRC。过表达 miR-183-5p 的外泌体可能是 CRC 的潜在治疗生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7db/7244076/8323455d6b38/aging-12-103145-g001.jpg

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