Exosomal miRNA-1231 derived from bone marrow mesenchymal stem cells inhibits the activity of pancreatic cancer
Exosomal miRNA-1231 derived from bone marrow mesenchymal stem cells inhibits the activity of pancreatic cancer
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骨髓间充质干细胞来源的外泌体miRNA-1231抑制胰腺癌活性
DOI：
10.1002/cam4.2633
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发表时间：
2019-10-23
期刊：
影响因子：
4
通讯作者：
Zuo, Chaohui
中科院分区：
文献类型：
--
作者：
Shang, Song;Wang, Jinfeng;Zuo, Chaohui
胰腺癌（Pancreatic cancer， PC）是一种发病率和死亡率都很高的恶性肿瘤，临床上诊断和治疗都很困难。骨髓间充质干细胞（bone marrow mesenchymal stem cells, BM-MSCs）通过分泌含有多种rna和蛋白质等生物分子的外泌体，影响免疫、炎症、肿瘤环境和肿瘤转移。在本研究中，来自外周血的外泌体中miRNA-1231 （miR-1231）的低表达与PC的TNM分期显著相关，提示外泌体miR-1231对PC的发生和发展有潜在的抑制作用。转染miR-1231寡核苷酸的BM-MSCs上清液衍生的外泌体可负调控PC细胞BxPC-3和PANC-1对基质的增殖、迁移、侵袭和粘附。同时，通过尾静脉注射来自转染miR-1231模拟物的BM-MSCs的外泌体，可以严重抑制BALB/C裸鼠体内的肿瘤生长。从BM-MSCs中提取的高水平miR-1231外泌体抑制了PC的活性，为开发新型高效的癌症治疗药物，特别是治疗PC提供了潜在的应用前景。外周血外泌体miR-1231也可能是未来PC诊断的潜在指标。
Pancreatic cancer (PC) is a highly malignant tumor with increased morbidity and mortality, which is difficult to diagnose and cure in the clinic. Through secreting exosomes containing biological molecules, including diverse RNAs and proteins, bone marrow mesenchymal stem cells (BM-MSCs) influence the immunity, inflammation, tumor environment, and cancer metastasis. In this study, low expression of miRNA-1231 (miR-1231) in exosomes derived from the peripheral blood was significantly correlated with the TNM stage of PC, suggesting the potential inhibitory effect of exosomal miR-1231 on PC occurrence and development. The proliferation, migration, invasion, and adhesion to the matrix of PC cells BxPC-3 and PANC-1 were negatively regulated by exosomes derived from the supernatants of BM-MSCs that transfected with miR-1231 oligonucleotides. Simultaneously, tumor growth in vivo was seriously restrained in BALB/C nude mice by tail vein injection with exosomes originated from BM-MSCs that transfected with miR-1231 mimics. The exosomes extracted from BM-MSCs with high level of miR-1231 inhibit the activity of PC, providing the potential application for developing new and efficient medicine for cancer therapy, especially for PC treatment. The exosomal miR-1231 of peripheral blood may also be a potential indicator for PC diagnosis in the future.