Ding Bo, Ye Zheng, Yin Han, Hong Xin-Yi, Feng Song-Wei, Xu Jing-Yun, Shen Yang
Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.
Genomics. 2023 Sep;115(5):110703. doi: 10.1016/j.ygeno.2023.110703. Epub 2023 Sep 9.
Cancer-associated fibroblast (CAF) is an essential risk factor for ovarian cancer. Exosomes can mediate cellular communication in the tumour microenvironment, but the interaction of tumour cell exosomes with CAF is less studied in Ovarian cancer. This study identified H19/miR-29c-3p/LOXL2-COL1A1 as a ceRNA regulatory network involved in regulating tumour matrix-associated signaling pathways associated with CAF. Cellular assays demonstrated that exosomes from ovarian cancer cell line SKOV3 significantly promoted the proliferation and migration of CAF. The results of mixed transplantation tumour experiments in nude mice showed that exosomes of SKOV3 significantly promoted tumour growth. Ovarian cancer tumour-derived exosomes can regulate CAF proliferation and migration through H19/miR-29c-3p/LOXL2-COL1A1. This study reveals the regulatory role of tumour exosomes on CAF, which may provide a theoretical basis for the development of therapeutic regimens targeting fibroblasts in ovarian cancer.
癌症相关成纤维细胞（CAF）是卵巢癌的一个重要危险因素。外泌体可介导肿瘤微环境中的细胞通讯，但肿瘤细胞外泌体与CAF的相互作用在卵巢癌中的研究较少。本研究确定H19/miR-29c-3p/LOXL2-COL1A1作为一种竞争性内源性RNA（ceRNA）调控网络，参与调节与CAF相关的肿瘤基质相关信号通路。细胞实验表明，卵巢癌细胞系SKOV3来源的外泌体显著促进了CAF的增殖和迁移。裸鼠混合移植瘤实验结果显示，SKOV3外泌体显著促进肿瘤生长。卵巢癌肿瘤来源的外泌体可通过H19/miR-29c-3p/LOXL2-COL1A1调节CAF的增殖和迁移。本研究揭示了肿瘤外泌体对CAF的调控作用，这可能为卵巢癌中针对成纤维细胞的治疗方案的开发提供理论依据。
