Ba Li, Xue Chunling, Li Xuechun, Zhang Mingjia, Yang Ying, Han Qin, Sun Zhao, Zhao Robert Chunhua
Beijing Key Laboratory (No. BZO381), Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing, P.R. China.
Department of Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, P.R. China.
Stem Cells Dev. 2021 Aug 15;30(16):830-842. doi: 10.1089/scd.2021.0059.
As an important component of the dynamic tumor microenvironment, mesenchymal stem cells (MSCs) can interact with tumor cells to promote tumor growth. Treatment with tumor cell-derived exosomes can change the biological functions of MSCs. We want to study the mechanism by which exosomes derived from gastric cancer cells affect the biological functions of MSCs. After MSCs were treated with adenocarcinoma gastric cells (AGS) cell-derived exosomes, circular RNAs differentially expressed in MSCs were verified using existing RNA microarray results combined with quantitative real-time polymerase chain reaction (qRT-PCR). Then, circular RNAs were knocked down or overexpressed by plasmids, and the functions of circular RNAs were evaluated by Migration and invasion assay. Dual luciferase reporter assay was used to evaluate the potential mechanism of circular RNAs. After treatment with exosomes secreted by AGS, the results showed that some circular RNAs expressed by human adipose-derived MSCs showed significant differences. The elevated circ_0004303 promoted the migration and invasion of human adipose-derived MSCs in vitro. Circ_0004303 upregulated the expression of activated leukocyte cell adhesion molecule (ALCAM) by acting as a miR-148a-3p sponge, thereby enhancing the migration and invasion functions of human adipose-derived MSCs. Therefore, exosomes secreted by AGS can affect the expression of circular RNAs in human adipose-derived MSCs. Hsa_circ_0004303 can regulate the migration and invasion of human adipose-derived MSCs via the miR-148a-3P/ALCAM axis. This study suggests that tumor cells can promote the migration and homing of MSCs in adjacent tissues by secreting exosomes.
作为动态肿瘤微环境的重要组成部分，间充质干细胞（MSCs）可与肿瘤细胞相互作用以促进肿瘤生长。用肿瘤细胞衍生的外泌体进行治疗可改变MSCs的生物学功能。我们想研究胃癌细胞衍生的外泌体影响MSCs生物学功能的机制。在用腺癌细胞（AGS）衍生的外泌体处理MSCs后，结合现有的RNA微阵列结果和定量实时聚合酶链反应（qRT-PCR）验证了MSCs中差异表达的环状RNA。然后，通过质粒敲低或过表达环状RNA，并通过迁移和侵袭试验评估环状RNA的功能。采用双荧光素酶报告基因试验评估环状RNA的潜在机制。用AGS分泌的外泌体处理后，结果显示人脂肪来源的MSCs表达的一些环状RNA有显著差异。升高的circ_0004303促进人脂肪来源的MSCs在体外的迁移和侵袭。Circ_0004303通过充当miR-148a-3p海绵上调活化白细胞细胞粘附分子（ALCAM）的表达，从而增强人脂肪来源的MSCs的迁移和侵袭功能。因此，AGS分泌的外泌体可影响人脂肪来源的MSCs中环状RNA的表达。Hsa_circ_0004303可通过miR-148a-3P/ALCAM轴调节人脂肪来源的MSCs的迁移和侵袭。本研究表明肿瘤细胞可通过分泌外泌体促进MSCs在邻近组织中的迁移和归巢。
