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人脐带间充质干细胞来源的外泌体携带 hsa-miRNA-128-3p 通过抑制半乳糖凝集素-3 抑制胰腺导管细胞癌。

Human umbilical cord mesenchymal stem cell-derived exosomes carrying hsa-miRNA-128-3p suppress pancreatic ductal cell carcinoma by inhibiting Galectin-3.

机构信息

Department of Gastroenterology, Affiliated Hospital and Medical School of Nantong University, Nantong, 226001, Jiangsu, China.

Office of Infection Management, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.

出版信息

Clin Transl Oncol. 2022 Mar;24(3):517-531. doi: 10.1007/s12094-021-02705-7. Epub 2021 Nov 23.

Abstract

BACKGROUND

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignant tumors of the digestive system. Many patients are diagnosed at an advanced stage and lose eligibility for surgery. Moreover, there are few effective methods for treating pancreatic ductal cell carcinoma. Increasing attention has been given to microRNAs (miRNAs) and their regulatory roles in tumor progression. In this study, we investigated the effects of exosomes extracted from human umbilical cord mesenchymal stem cells (HUCMSCs) carrying hsa-miRNA-128-3p on pancreatic cancer cells.

METHODS

Based on existing experimental and database information, we selected Galectin-3, which is associated with pancreatic cancer, and the corresponding upstream hsa-miRNA-128-3p. We extracted HUCMSCs from a fresh umbilical cord, hsa-miRNA-128-3p was transfected into HUCMSCs, and exosomes containing hsa-miRNA-128-3p were extracted and collected. The effect of exosomes rich in hsa-miRNA-128-3p on pancreatic cancer cells was analyzed.

RESULTS

The expression of Galectin-3 in normal pancreatic duct epithelial cells was significantly lower than that in PDAC cell lines. We successfully extracted HUCMSCs from the umbilical cord and transfected hsa-miRNA-128-3p into HUCMSCs. Then we demonstrated that HUCMSC-derived exosomes with hsa-miRNA-128-3p could suppress the proliferation, invasion, and migration of PANC-1 cells in vitro by targeting Galectin-3.

CONCLUSION

Hsa-miRNA-128-3p could be considered as a potential therapy for pancreatic cancer. We provided a new idea for targeted therapy of PDAC.

摘要

背景

胰腺导管腺癌(PDAC)是消化系统最致命的恶性肿瘤之一。许多患者在晚期被诊断出来,失去了手术的资格。此外,治疗胰腺导管细胞癌的有效方法很少。人们越来越关注 microRNAs(miRNAs)及其在肿瘤进展中的调节作用。在这项研究中,我们研究了携带 hsa-miRNA-128-3p 的人脐带间充质干细胞(HUCMSCs)提取的外泌体对胰腺癌细胞的影响。

方法

基于现有的实验和数据库信息,我们选择了与胰腺癌相关的 Galectin-3 及其对应的上游 hsa-miRNA-128-3p。我们从新鲜的脐带中提取 HUCMSCs,将 hsa-miRNA-128-3p 转染到 HUCMSCs 中,提取并收集富含 hsa-miRNA-128-3p 的外泌体。分析富含 hsa-miRNA-128-3p 的外泌体对胰腺癌细胞的影响。

结果

正常胰腺导管上皮细胞中 Galectin-3 的表达明显低于 PDAC 细胞系。我们成功地从脐带中提取了 HUCMSCs,并将 hsa-miRNA-128-3p 转染到 HUCMSCs 中。然后我们证明了 HUCMSC 衍生的含有 hsa-miRNA-128-3p 的外泌体可以通过靶向 Galectin-3 抑制 PANC-1 细胞的体外增殖、侵袭和迁移。

结论

hsa-miRNA-128-3p 可被视为治疗胰腺癌的一种潜在疗法。我们为 PDAC 的靶向治疗提供了一个新的思路。

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