Zhou Linsen, Zhang Xinyi, Wang Zhiqiang, Li Dongqing, Zhou Guangjun, Liu Haofeng
Department of General Surgery, The Yancheng Clinical College of Xuzhou Medical University and The First people's Hospital of Yancheng, Yancheng, Jiangsu Province, 224001, China.
Department of General Surgery, Tumor Hospital Affiliated to Nantong University and Nantong Tumor Hospital, No.30, Tongyang North Road, Pingchao Town, Tongzhou District, Nantong, Jiangsu Province, 226361, China.
Cancer Cell Int. 2024 Oct 1;24(1):330. doi: 10.1186/s12935-024-03493-0.
As colorectal cancer (CRC) remains one of the leading causes of cancer-related deaths, understanding novel therapeutic mechanisms is crucial. This research focuses on the role of extracellular vesicles (EVs) from bone marrow stromal cells (BMSCs) in delivering miR-766-3p to CRC cells, targeting the MYC/CDK2 signaling axis.
Differentially expressed genes between BMSCs-EVs and CRC were identified using the Gene Expression Omnibus database. miR-766-3p target genes were predicted via TargetScan and RNAInter, with protein interactions analyzed using the STRING database. The analysis included RT-qPCR and Western blot on samples from 52 CRC patients. Characterization of BMSCs-EVs was followed by their functional assessment on CRC cell lines and the normal colon cell line CCD-18CO, evaluating cellular uptake, proliferation, migration, invasion, and apoptosis.
miR-766-3p was confirmed in BMSCs-EVs and found underexpressed in CRC. BMSCs-EVs transported miR-766-3p to CRC cells, inhibiting their proliferation, migration, and invasion while promoting apoptosis. miR-766-3p targeted MYC, leading to decreased CDK2 transcription. Overexpression of MYC in HCT-116 cells counteracted these effects. In vivo studies showed that BMSCs-EVs carrying miR-766-3p hindered tumor growth.
The study demonstrates the efficacy of BMSCs-EVs in delivering miR-766-3p to CRC cells, leading to the suppression of the MYC/CDK2 signaling pathway and hindering cancer progression.
由于结直肠癌（CRC）仍然是癌症相关死亡的主要原因之一，了解新的治疗机制至关重要。本研究聚焦于骨髓基质细胞（BMSC）来源的细胞外囊泡（EV）在向CRC细胞递送miR-766-3p并靶向MYC/CDK2信号轴方面的作用。
使用基因表达综合数据库鉴定BMSC-EV和CRC之间的差异表达基因。通过TargetScan和RNAInter预测miR-766-3p的靶基因，并使用STRING数据库分析蛋白质相互作用。分析包括对52例CRC患者样本进行逆转录定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹法（Western blot）。对BMSC-EV进行表征后，在CRC细胞系和正常结肠细胞系CCD-18CO上对其进行功能评估，评估细胞摄取、增殖、迁移、侵袭和凋亡情况。
在BMSC-EV中证实存在miR-766-3p，且在CRC中发现其表达下调。BMSC-EV将miR-766-3p转运至CRC细胞，抑制其增殖、迁移和侵袭，同时促进凋亡。miR-766-3p靶向MYC，导致CDK2转录减少。在HCT-116细胞中过表达MYC可抵消这些作用。体内研究表明，携带miR-766-3p的BMSC-EV可抑制肿瘤生长。
该研究证明了BMSC-EV在向CRC细胞递送miR-766-3p方面的有效性，导致MYC/CDK2信号通路受到抑制并阻碍癌症进展。
