miR-31-modified bone marrow mesenchymal stem cells facilitate autophagic cell death of colorectal cancer via binding to CCR7 to modulate PI3K/Akt/mTOR signals.

[BACKGROUND] Autophagic cell death plays a complex role in colorectal cancer (CRC) progression. MicroRNA-31 (miR-31) is implicated in tumor regulation, and bone marrow mesenchymal stem cells (BMSCs) show promise as targeted delivery vehicles for cancer therapy. However, the effect and mechanism of miR-31-modified BMSCs on autophagic cell death in CRC cells remain unclear.

[OBJECTIVE] This study aimed to explore the effect and underlying mechanism of miR-31-modified BMSCs on inducing autophagic cell death in colorectal cancer cells.

[METHODS] HT29 colorectal cancer cells were divided into multiple groups: Control, miR-31 mimic, BMSCs co-culture, miR-31-modified BMSCs co-culture, CCR7 overexpression, and combined treatment groups. Key indicators were detected using RT-qPCR, Western blot, and flow cytometry to analyze gene expression, protein levels, and autophagic cell death.

[RESULTS] MiR-31-modified BMSCs significantly elevated miR-31 levels and suppressed CCR7 expression in HT29 cells. Compared to the control group, this treatment significantly increased autophagic cell death (22.84% vs. 6.72%), upregulated the autophagy markers LC3-II and Beclin-1, and inhibited phosphorylation of key proteins in the PI3K/Akt/mTOR pathway. Overexpression of CCR7 effectively reversed these pro-autophagic and signaling inhibitory effects.

[CONCLUSION] MiR-31-modified BMSCs induce autophagic cell death in colorectal cancer cells by delivering miR-31 to target and inhibit CCR7, thereby suppressing the PI3K/Akt/mTOR signaling pathway. This study provides a novel strategic foundation for BMSC-based gene therapy in colorectal cancer.