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