Extracellular vesicle-mediated delivery of miR-766-3p from bone marrow stromal cells as a therapeutic strategy against colorectal cancer.

IF 5.3 2区医学 Q1 ONCOLOGY Cancer Cell International Pub Date : 2024-10-01 DOI:10.1186/s12935-024-03493-0

Linsen Zhou, Xinyi Zhang, Zhiqiang Wang, Dongqing Li, Guangjun Zhou, Haofeng Liu

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Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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以细胞外囊泡为媒介从骨髓基质细胞中输送 miR-766-3p 作为结直肠癌治疗策略。

目的：结直肠癌（CRC）仍然是癌症相关死亡的主要原因之一，因此了解新的治疗机制至关重要。本研究的重点是骨髓基质细胞（BMSCs）的胞外囊泡（EVs）在向CRC细胞传递miR-766-3p、靶向MYC/CDK2信号轴中的作用：通过 TargetScan 和 RNAInter 预测 miR-766-3p 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 RT-qPCR 和 Western 印迹。在对 BMSCs-EVs 进行表征后，还对其在 CRC 细胞系和正常结肠细胞系 CCD-18CO 上的功能进行了评估，评估了细胞吸收、增殖、迁移、侵袭和凋亡。BMSCs-EVs 将 miR-766-3p 运送到 CRC 细胞，抑制其增殖、迁移和侵袭，同时促进细胞凋亡。在 HCT-116 细胞中过表达 MYC 可抵消这些效应。体内研究表明，携带miR-766-3p的BMSCs-EV阻碍了肿瘤的生长：研究表明，BMSCs-EVs 能有效地向 CRC 细胞传递 miR-766-3p，从而抑制 MYC/CDK2 信号通路，阻碍癌症进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.