Fang Yaohui, Tan Chunlu, Zheng Zhenjiang, Yang Jianchen, Tang Jiali, Guo Ruizhe, Silli Epiphane K, Chen Zhe, Chen Jia, Ge Ruyu, Liu Yuquan, Wen Xiuqi, Liang Jingdan, Zhu Yunfei, Jin Yutong, Li Qian, Wang Ying
College of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 211198, China.
Department of Pancreatic Surgery and General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Biochem Pharmacol. 2025 Jun;236:116849. doi: 10.1016/j.bcp.2025.116849. Epub 2025 Mar 6.
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignant tumor characterized by a poor prognosis. A prominent feature of PDAC is the rich and dense stroma present in the tumor microenvironment (TME), which significantly hinders drug penetration. Cancer-associated fibroblasts (CAFs), activated fibroblasts originating from various cell sources, including pancreatic stellate cells (PSCs) and mesenchymal stem cells (MSCs), play a critical role in PDAC progression and TME formation. MicroRNAs (miRNAs) are small, single-stranded non-coding RNA molecules that are frequently involved in tumorigenesis and progression, exhibiting either oncolytic or oncogenic activity. Increasing evidence suggests that aberrant expression of miRNAs can mediate interactions between cancer cells and CAFs, thereby providing novel therapeutic targets for PDAC treatment. In this review, we will focus on the potential roles of miRNAs that target CAFs or CAFs-derived exosomes in PDAC progression, highlighting the feasibility of therapeutic strategies aimed at restoring aberrantly expressed miRNAs associated with CAFs, offering new pathways for the clinical management of PDAC.
胰腺导管腺癌（PDAC）是一种预后较差的高致死性恶性肿瘤。PDAC的一个显著特征是肿瘤微环境（TME）中存在丰富且致密的基质，这显著阻碍了药物渗透。癌症相关成纤维细胞（CAFs）是源自包括胰腺星状细胞（PSCs）和间充质干细胞（MSCs）在内的各种细胞来源的活化成纤维细胞，在PDAC进展和TME形成中起关键作用。微小RNA（miRNAs）是小的单链非编码RNA分子，经常参与肿瘤发生和进展，表现出溶瘤或致癌活性。越来越多的证据表明，miRNAs的异常表达可介导癌细胞与CAFs之间的相互作用，从而为PDAC治疗提供新的治疗靶点。在本综述中，我们将重点关注靶向CAFs或CAFs衍生外泌体的miRNAs在PDAC进展中的潜在作用，强调旨在恢复与CAFs相关的异常表达miRNAs的治疗策略的可行性，为PDAC的临床管理提供新途径。
