Anticancer effects of miR-124 delivered by BM-MSC derived exosomes on cell proliferation, epithelial mesenchymal transition, and chemotherapy sensitivity of pancreatic cancer cells.
Anticancer effects of miR-124 delivered by BM-MSC derived exosomes on cell proliferation, epithelial mesenchymal transition, and chemotherapy sensitivity of pancreatic cancer cells.
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DOI：
10.18632/aging.103997
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发表时间：
2020-10-11
期刊：
影响因子：
--
通讯作者：
Shi B
中科院分区：
文献类型：
--
作者：
Xu Y;Liu N;Wei Y;Zhou D;Lin R;Wang X;Shi B
目的：本研究旨在探讨miR-124在胰腺肿瘤及其潜在载体中的作用。结果：miR-124在胰腺腺癌组织及细胞系AsPC-1、PANC1、BxPC-3、SW1990中表达水平降低。此外，通过miR-124模拟转染诱导的凋亡、转移和上皮间质转化，miR-124在AsPC-1和PANC1中的表达升高被抑制，EZH2过表达部分逆转了miR-124对胰腺肿瘤的保护作用。此外，在miR-124转染的BM-MSCs中提取的外泌体中检测到miR-124的表达，这些外泌体将miR-124递送到胰腺癌细胞中，并在体外和体内表现出抗肿瘤作用。结论：携带mir -124的bm - msc衍生外泌体在胰腺肿瘤的治疗中具有潜在的应用前景。方法：检测miR-124和EZH2在胰腺癌组织和细胞系中的表达。miR-124或EZH2在AsPC-1和PANC1细胞中过表达。然后是对细胞活力的影响。观察细胞凋亡、侵袭、迁移和上皮间质转化。随后，通过双荧光素酶报告基因法检测miR-124在胰腺肿瘤中对EZH2表达和功能的影响。随后，将miR-124转染到骨髓间充质基质细胞（BM-MSCs）中，分离BM-MSCs衍生的外泌体，与AsPC-1和PANC1细胞共培养，或注射到胰腺癌荷瘤小鼠体内。
Objective: This study aims to explore the roles of miR-124 in pancreatic tumor and potential vehicles. Results: The miR-124 expression levels decreased in pancreatic adenocarcinoma tissues and cancer cell lines AsPC-1, PANC1, BxPC-3 and SW1990. Furthermore, the elevated expression of miR-124 in AsPC-1 and PANC1 via miR-124 mimic transfection-induced apoptosis, metastasis and epithelial mesenchymal transition was suppressed, and the EZH2 overexpression partly reversed the protective effects of miR-124 against pancreatic tumors. In addition, the expression of miR-124 was detected in exosomes extracted from miR-124-transfected BM-MSCs, and these exosomes delivered miR-124 into pancreatic cancer cells, and presented the anti-tumor effects in vitro and in vivo. Conclusion: MiR-124-carried BM-MSC-derived exosomes have potential applications for the treatment of pancreatic tumors. Methods: The expression of miR-124 and EZH2 was determined in both pancreatic cancer tissues and cell lines. miR-124 or EZH2 was overexpressed in AsPC-1 and PANC1 cells. Then, the effects on cell viability. apoptosis, invasion, migration and epithelial mesenchymal transition were evaluated. Afterwards, the roles of miR-124 on the expression and function of EZH2 in pancreatic tumors were determined by dual luciferase reporter assay. Subsequently, miR-124 was transfected to bone marrow mesenchymal stromal cells (BM-MSCs), and the BM-MSCs derived exosomes were isolated and co-cultured with AsPC-1 and PANC1 cells, or injected into pancreatic cancer tumor-bearing mice.
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DOI：
10.1074/jbc.m113.525493
发表时间：
2014-07-25
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Neo WH;Yap K;Lee SH;Looi LS;Khandelia P;Neo SX;Makeyev EV;Su IH
通讯作者：
Su IH
影响因子：
82.9
作者：
Huang, Ling;Holtzinger, Audrey;Muthuswamy, Senthil K.
通讯作者：
Muthuswamy, Senthil K.
影响因子：
--
作者：
Jiang T;Wang Y;Zhou F;Gao G;Ren S;Zhou C
通讯作者：
Zhou C
影响因子：
3.3
作者：
Du, Jing;He, Yuanqiao;Han, Yong
通讯作者：
Han, Yong
影响因子：
64.8
作者：
Margueron, Raphael;Reinberg, Danny
通讯作者：
Reinberg, Danny