人脐带间充质干细胞来源的外泌体通过miRNAs促进胰腺癌细胞生长  

Exosomes secreted from human umbilical cord mesenchymal stem cells promote pancreatic ductal adenocarcinoma growth by transferring miRNAs

作　　者：丁乙轩 王宇婷 梅文通 郑智 曲元旭 梁阔[1] 李嘉[1] 曹锋[1] 李非[1] Ding Yixuan;Wang Yuting;Mei Wentong;Zheng Zhi;Qu Yuanxu;Liang Kuo;Li Jia;Cao Feng;Li Fei(Department of General Surgery,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;Capital Medical University,Clinical Medicine College,Beijing 100069,China)

机构地区：[1]首都医科大学宣武医院普通外科,北京100053 [2]首都医科大学临床医学院,北京100069

出　　处：《中华肿瘤杂志》2023年第1期50-55,共6页Chinese Journal of Oncology

基　　金：首都临床特色应用研究与成果推广项目(Z171100001017077);首都临床诊疗技术研究及示范应用专项(Z191100006619038);首都医科大学临床医学高精尖学科建设项目(1192070312);北京市医院管理局临床医学发展专项经费资助(XMLX201404);北京市自然科学基金(7182063)。

摘　　要：目的探讨人脐带间充质干细胞来源的外泌体(hucMSCs-exo)对胰腺癌细胞增殖、侵袭的影响及其分子机制。方法 hucMSCs-exo来自首都医科大学宣武医院顺利分娩后的产妇(3例,脐带长约20 cm),将hucMSCs-exo分别加入胰腺癌细胞BxPC3和Panc-1中,采用细胞计数试剂盒8(CCK-8)法和Transwell实验检测BxPC3和Panc-1细胞的增殖和侵袭能力。小鼠皮下接种人胰腺癌Panc-1细胞(1×106个),hucMSCs-exo组小鼠直接于肿瘤内注射hucMSCs-exo,对照组注射磷酸盐缓冲液,测量小鼠模型肿瘤的体积及重量。采用高通量测序方法检测外泌体中miRNAs的表达,通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析高表达miRNAs的靶基因相关功能以及主要代谢通路。结果 CCK-8实验显示,hucMSCs-exo组BxPC3和Panc-1细胞吸光度值分别为4.68±0.09和5.20±0.20,高于Control组(分别为3.68±0.01和3.45±0.17,均P<0.05)。Transwell实验显示,hucMSCs-exo组BxPC3和Panc-1细胞侵袭数分别为(129.40±6.02)个和(134.40±7.02)个,高于Control组[分别为(89.40±4.39)个和(97.00±6.08)个,均P<0.05]。hucMSCs-exo组肿瘤体积[(884.57±59.70)mm3]和肿瘤质量[(0.94±0.21)g]均高于Control组[分别为(695.09±57.81)mm3和(0.60±0.13)g,均P<0.05]。高通量测序结果显示,hucMSCs-exo中miR-148a-3p、miR-100-5p、miR-143-3p、miR-21-5p和miR-92a-3p呈高表达,GO以及KEGG分析结果显示,高表达miRNAs的靶基因主要参与调节细胞葡萄糖醛酸化,主要代谢通路是抗坏血酸和醛酸代谢。结论 hucMSCs-exo可促进胰腺癌细胞的生长,其机制与外泌体中高表达的miRNAs相关。Objective To observe the effects of exosomes derived from human umbilical cord mesenchymal stem cells on the proliferation and invasion of pancreatic cancer cells,and to analyze the contents of exosomes and explore the mechanisms affecting pancreatic cancer cells.Methods Exosomes extracted from human umbilical cord mesenchymal stem cells were added to pancreatic cancer cells BxPC3,Panc-1 and mouse models of pancreatic cancer,respectively.The proliferative activity and invasion abilities of BxPC3 and Panc-1 cells were measured by cell counting kit-8(CCK-8)and Transwell assays.The expressions of miRNAs in exosomes were detected by high-throughput sequencing.GO and KEGG were used to analyze the related functions and the main metabolic pathways of target genes with high expressions of miRNAs.Results The results of CCK-8 cell proliferation assay showed that the absorbance of BxPC3 and Panc-1 cells in the hucMSCs-exo group was significantly higher than that in the control group[(4.68±0.09)vs.(3.68±0.01),P<0.05;(5.20±0.20)vs.(3.45±0.17),P<0.05].Transwell test results showed that the number of invasion cells of BxPC3 and Panc-1 in hucMSCs-exo group was significantly higher than that in the control group(129.40±6.02)vs.(89.40±4.39),P<0.05;(134.40±7.02)vs.(97.00±6.08),P<0.05.In vivo experimental results showed that the tumor volume and weight in the exosomes derived from human umbilical cord mesenchymal stem cells(hucMSCs-exo)group were significantly greater than that in the control group[(884.57±59.70)mm3 vs.(695.09±57.81)mm3,P<0.05;(0.94±0.21)g vs.(0.60±0.13)g,P<0.05].High-throughput sequencing results showed that miR-148a-3p,miR-100-5p,miR-143-3p,miR-21-5p and miR-92a-3p were highly expressed.GO and KEGG analysis showed that the target genes of these miRNAs were mainly involved in the regulation of glucosaldehylation,and the main metabolic pathways were ascorbic acid and aldehyde acid metabolism,which were closely related to the development of pancreatic cancer.Conclusion Exosomes derived from human umbilica

关 键 词：胰腺肿瘤 人脐带间充质干细胞 外泌体 MIRNAS 

分 类 号：R735.9[医药卫生—肿瘤]