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

Abstract

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.

Keywords

• Colorectal cancer
• Bone marrow stromal cells
• Extracellular vesicles
• miR-766-3p
• MYC
• CDK2