肿瘤相关成纤维细胞来源外泌体ciRS-7经miR-7/IGF1R轴促进胰腺癌细胞糖酵解

目的：探讨肿瘤相关成纤维细胞（CAFs）来源外泌体ciRS-7对胰腺癌细胞糖酵解代谢的影响。方法：采用超速离心法提取CAFs外泌体，并通过实时定量聚合酶链反应（RT-qPCR）检测外泌体中ciRS-7的表达及胰腺癌细胞糖酵解关键酶mRNA的表达；构建含ciRS-7 野生及突变序列的荧光素酶检测报告质粒，在胰腺癌细胞中验证ciRS-7与miR-7的关系；蛋白质印迹（Western blot）法检测IGF1R/AKT蛋白表达。结果：ciRS-7在胰腺癌相关成纤维细胞的外泌体中表达上调（P ＜0.05）；CAFs释放的外泌体促进胰腺癌细胞糖酵解和增殖（P ＜0.05）；敲降胰腺癌相关成纤维细胞ciRS-7的表达，其外泌体可抑制胰腺癌细胞糖酵解相关基因的表达（P ＜0.05）；ciRS-7在胰腺癌细胞中经miR-7/IGF1R/AKT通路促进癌细胞糖酵解（P ＜0.05）。结论：ciRS-7在胰腺癌相关成纤维细胞的外泌体中高表达，下调ciRS-7具有抑制胰腺癌细胞糖酵解的作用。

The inhibiting effect of exosomal ciRS-7 derived from cancer associated fibroblasts on glycolysis of pancreatic cancer cells via miR-7/IGF1R axis

Objective: To investigate the effect of exosomal ciRS-7 derived from cancer associated fibroblasts (CAFs) on glycolysis of pancreatic cancer cells. Methods: Exosomes derived from CAFs were extracted by ultracentrifugation, and the real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of exosomal ciRS-7 and the mRNAs of key glycolytic enzymes in pancreatic cancer cells.ciRS-7-WT or ciRS-7-MT was used to verify the relationship between ciRS-7 and miR-7 in pancreatic cancer by Dual Luciferase Reporter Assay. The protein changes of IGF1R/AKT axis in pancreatic cancer were analyzed by Western blot. Results: The expression of ciRS-7 was up-regulated in the exosomes derived from CAFs. The exosomes released by CAFs promoted glycolytic metabolism and proliferation of pancreatic cancer cells. The exosomes released by pancreatic CAFs with ciRS-7 knock-down could inhibit the expression of glycolysis-related genes in pancreatic cancer cells. And ciRS-7 promoted glycolysis in pancreatic cancer cells through modulating the miR7/IGF1R/AKT pathway. Conclusion: Exosomal ciRS-7 was up-regulated in pancreatic CAFs, and the downregulation of ciRS-7 expression in CAFs could suppress the glycolysis metabolism in pancreatic cancer cells.