Zhang Shuairan, Liu Shiqi, Dong Hang, Jin Xiuli, Sun Jing, Sun Ji, Wu Gang, Li Yiling
Department of Gastroenterology, The First Hospital of China Medical University, Shenyang, PR China.
Department of Hepatobiliary Surgery, The First Hospital of China Medical University, Shenyang, PR China.
Hepatol Commun. 2025 Jan 7;9(1). doi: 10.1097/HC9.0000000000000616. eCollection 2025 Jan 1.
Accumulating evidence suggests that microRNAs derived from macrophage exosomes can regulate the stemness and progression of cancer. However, the interaction mechanisms between HCC cells and tumor-associated macrophages remain unclear.
Exosomes were extracted from control or CD63 overexpression macrophages and co-cultured with HCC cells. The stemness, proliferation, epithelial-mesenchymal transition, and in vivo tumorigenicity of HCC cells were assessed to determine the role of CD63-high macrophage-derived exosomal miR-6876-5p in HCC. The binding relationship between miR-6876-5p and the PTEN/Akt axis was also investigated.
Elevated CD63 expression was associated with increased tumor-associated macrophage infiltration and poorer prognosis in HCC. CD63-high macrophage-derived exosomes enhanced HCC cell proliferation, stemness, and epithelial-mesenchymal transition. miR-6876-5p within these exosomes was identified as a key mediator, promoting HCC progression by targeting PTEN and activating the Akt signaling pathway. In vivo studies confirmed that CD63-high macrophage-derived exosomal miR-6876-5p accelerated tumor growth and enhanced stemness in HCC cells.
CD63-high macrophage-derived exosomes, particularly those enriched with miR-6876-5p, play a pivotal role in HCC progression by enhancing stemness and promoting epithelial-mesenchymal transition through the PTEN/Akt pathway. Targeting these exosomes and their microRNAs offers a promising therapeutic strategy forHCC.
越来越多的证据表明，源自巨噬细胞外泌体的微小RNA可调节癌症的干性和进展。然而，肝癌细胞与肿瘤相关巨噬细胞之间的相互作用机制仍不清楚。
从对照或CD63过表达巨噬细胞中提取外泌体，并与肝癌细胞共培养。评估肝癌细胞的干性、增殖、上皮-间质转化和体内致瘤性，以确定CD63高表达巨噬细胞衍生的外泌体miR-6876-5p在肝癌中的作用。还研究了miR-6876-5p与PTEN/Akt轴之间的结合关系。
CD63表达升高与肝癌中肿瘤相关巨噬细胞浸润增加和预后较差相关。CD63高表达巨噬细胞衍生的外泌体增强了肝癌细胞的增殖、干性和上皮-间质转化。这些外泌体中的miR-6876-5p被确定为关键介质，通过靶向PTEN和激活Akt信号通路促进肝癌进展。体内研究证实，CD63高表达巨噬细胞衍生的外泌体miR-6876-5p加速了肿瘤生长并增强了肝癌细胞的干性。
CD63高表达巨噬细胞衍生的外泌体，特别是富含miR-6876-5p的外泌体，通过增强干性并通过PTEN/Akt途径促进上皮-间质转化，在肝癌进展中起关键作用。靶向这些外泌体及其微小RNA为肝癌提供了一种有前景的治疗策略。
