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外泌体传递的miRNA-335-5p通过靶向RASA1促进上皮-间质转化,从而促进结直肠癌的侵袭和转移。

Exosome-transmitted miRNA-335-5p promotes colorectal cancer invasion and metastasis by facilitating EMT via targeting RASA1.

作者信息

Sun Xuecheng, Lin Feiyan, Sun Wenjing, Zhu Weijian, Fang Daoquan, Luo Lifang, Li Shuhan, Zhang Wenqi, Jiang Lei

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.

State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.

出版信息

Mol Ther Nucleic Acids. 2021 Feb 24;24:164-174. doi: 10.1016/j.omtn.2021.02.022. eCollection 2021 Jun 4.

DOI:10.1016/j.omtn.2021.02.022
PMID:33767913
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7960496/
Abstract

Exosomal microRNA (miRNA) secretion has been characterized as a vital factor in intercellular communication among cancer cells. However, little is known about cancer-secreted miRNAs specifically involved in metastasis of colorectal cancer (CRC). Here, we found that exosomes derived from metastatic CRC cell line SW620 promoted migration, invasion, and epithelial-mesenchymal transition (EMT) of CRC cells. The profiling of exosome miRNAs revealed that microRNA (miR)-335-5p was highly expressed in exosomes from metastatic SW620 cells compared to those derived from primary SW480 cells. miR-335-5p was transmitted from metastatic SW620 cells to CRC cells via exosomes and promoted migration, invasion, and EMT of CRC cells. Moreover, exosome-transmitted miRNA-335-5p promotes CRC cell invasion and metastasis by facilitating EMT via targeting RAS p21 protein activator 1 (). Overexpression of abolished the promotive effects of exosomal miR-335-5p on CRC cell migration, invasion, and EMT. Collectively, our data revealed that exosomal miR-335-5p derived from metastatic CRC cells promotes CRC cell invasion and metastasis by facilitating EMT via targeting , which may serve as a potential therapeutic target for CRC metastasis.

摘要

外泌体微小RNA(miRNA)分泌已被视为癌细胞间细胞通讯的关键因素。然而,对于特异性参与结直肠癌(CRC)转移的癌症分泌型miRNA却知之甚少。在此,我们发现源自转移性CRC细胞系SW620的外泌体可促进CRC细胞的迁移、侵袭及上皮-间质转化(EMT)。外泌体miRNA分析显示,与源自原发性SW480细胞的外泌体相比,转移性SW620细胞来源的外泌体中微小RNA(miR)-335-5p高表达。miR-335-5p通过外泌体从转移性SW620细胞传递至CRC细胞,并促进CRC细胞的迁移、侵袭及EMT。此外,外泌体传递的miRNA-335-5p通过靶向RAS p21蛋白激活因子1促进EMT,从而促进CRC细胞侵袭和转移。的过表达消除了外泌体miR-335-5p对CRC细胞迁移、侵袭及EMT的促进作用。总体而言,我们的数据表明,源自转移性CRC细胞的外泌体miR-335-5p通过靶向促进EMT,从而促进CRC细胞侵袭和转移,这可能成为CRC转移的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0399/7960496/15deb6d898d5/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0399/7960496/c2f956983b02/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0399/7960496/53d3dfe55350/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0399/7960496/c45b0fe5f2a4/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0399/7960496/a20ff1f99ff4/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0399/7960496/636219c5e107/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0399/7960496/9ddfd9ad1e55/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0399/7960496/15deb6d898d5/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0399/7960496/c2f956983b02/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0399/7960496/53d3dfe55350/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0399/7960496/c45b0fe5f2a4/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0399/7960496/a20ff1f99ff4/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0399/7960496/636219c5e107/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0399/7960496/9ddfd9ad1e55/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0399/7960496/15deb6d898d5/gr6.jpg

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