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.

中文翻译：

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胃癌细胞来源的外泌体可通过诱导环状RNA circ_0004303的表达来调节间充质干细胞的生物学功能

作为动态肿瘤微环境的重要组成部分，间充质干细胞（MSCs）可以与肿瘤细胞相互作用，促进肿瘤生长。用肿瘤细胞衍生的外泌体治疗可以改变 MSCs 的生物学功能。我们想研究来自胃癌细胞的外泌体影响MSCs生物学功能的机制。在用腺癌细胞（AGS）细胞衍生的外泌体处理MSCs后，使用现有的RNA微阵列结果结合定量实时聚合酶链反应（qRT-PCR）验证MSCs中差异表达的环状RNA。然后，环状RNA被质粒敲低或过表达，并通过迁移和侵袭测定评估环状RNA的功能。双荧光素酶报告基因检测用于评估环状 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表现出显着差异。升高的 circ_0004303 促进了体外人脂肪来源的 MSCs 的迁移和侵袭。Circ_0004303 通过充当 miR-148a-3p 海绵上调活化白细胞粘附分子 (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 分泌的外泌体可以影响人类脂肪来源的 MSCs 中环状 RNA 的表达。Hsa_circ_0004303 可以通过 miR-148a-3P/ALCAM 轴调节人类脂肪来源的 MSCs 的迁移和侵袭。