癌症相关成纤维细胞 (CAF) 是肿瘤微环境中的主要细胞成分，并已被证明在肝细胞癌 (HCC) 中表现出促肿瘤作用。本研究旨在深入探讨 CA​​F 在 HCC 中促肿瘤作用的机制。通过小RNA测序来筛选来自CAF和正常成纤维细胞（NF）的外泌体中差异表达的microRNA。然后使用逆转录酶定量实时 PCR 测量 CAF、NF、CAF 衍生的外泌体 (CAFs-Exo) 和 NF 衍生的外泌体 (NFs-Exo) 中的 miR-92a-3p 表达。与NFs或NF-Exo相比，CAFs和CAFs-Exo显着促进HCC细胞增殖、迁移和干性。此外，与 NF 或 NF-Exo 相比，CAF 和 CAF-Exo 中的 miR-92a-3p 水平分别显着较高。研究发现外泌体 miR-92a-3p 可以增强 HCC 细胞的增殖、迁移和干性。同时，AXIN1 被 miR-92a-3p 靶向。外泌体 miR-92a-3p 可以通过抑制 AXIN1 信使 RNA 来激活 HCC 细胞中的 β-catenin/CD44 信号传导。此外，体内研究证实外泌体 miR-92a-3p 通过靶向 AXIN1/β-catenin 轴显着促进肿瘤生长和干性。总的来说，CAF 分泌的外泌体 miR-92a-3p 能够通过抑制 AXIN1 激活 Wnt/β-catenin 信号通路来促进 HCC 的生长和干性。因此，靶向 CAF 衍生的 miR-92a-3p 可能是治疗 HCC 的潜在策略。© 2024 Wiley periodicals LLC。

Cancer-associated fibroblasts (CAFs) are a major cellular component in the tumor microenvironment and have been shown to exhibit protumorigenic effects in hepatocellular carcinoma (HCC). This study aimed to delve into the mechanisms underlying the tumor-promoting effects of CAFs in HCC. Small RNA sequencing was conducted to screen differential expressed microRNAs in exosomes derived from CAFs and normal fibroblasts (NFs). The miR-92a-3p expression was then measured using reverse transcriptase quantitative real-time PCR in CAFs, NFs, CAFs-derived exosomes (CAFs-Exo), and NF-derived exosomes (NFs-Exo). Compared to NFs or NF-Exo, CAFs and CAFs-Exo significantly promoted HCC cell proliferation, migration, and stemness. Additionally, compared to NFs or NF-Exo, miR-92a-3p level was notably higher in CAFs and CAFs-Exo, respectively. Exosomal miR-92a-3p was found to enhance HCC cell proliferation, migration, and stemness. Meanwhile, AXIN1 was targeted by miR-92a-3p. Exosomal miR-92a-3p could activate β-catenin/CD44 signaling in HCC cells by inhibiting AXIN1 messenger RNA. Furthermore, in vivo studies verified that exosomal miR-92a-3p notably promoted tumor growth and stemness through targeting AXIN1/β-catenin axis. Collectively, CAFs secreted exosomal miR-92a-3p was capable of promoting growth and stemness in HCC through activation of Wnt/β-catenin signaling pathway by suppressing AXIN1. Therefore, targeting CAFs-derived miR-92a-3p may be a potential strategy for treating HCC.© 2024 Wiley Periodicals LLC.