1. Innovative Therapeutic Delivery of Metastasis-Associated in Colon Cancer 1-Suppressing miRNA Using High Transmembrane 4 L6 Family Member 5-Targeting Exosomes in Colorectal Cancer Mouse Models.
- Author
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Choi BJ, Lee D, Park JH, Hong TH, Kim OH, Lee SC, Kim KH, Choi HJ, and Kim SJ
- Subjects
- Animals, Humans, Mice, Xenograft Model Antitumor Assays, Trans-Activators genetics, Trans-Activators metabolism, HCT116 Cells, Membrane Proteins metabolism, Membrane Proteins genetics, Gene Expression Regulation, Neoplastic, Disease Models, Animal, Cell Line, Tumor, Apoptosis, Mice, Nude, MicroRNAs genetics, Colorectal Neoplasms pathology, Colorectal Neoplasms genetics, Colorectal Neoplasms metabolism, Colorectal Neoplasms therapy, Exosomes metabolism, Exosomes genetics
- Abstract
Elevated metastasis-associated in colon cancer 1 (MACC1) expression in colorectal cancer patients, and high transmembrane 4 L6 family member 5 (TM4SF5) protein expressed on various solid tumors' surface, are linked to aggressive cancer behavior and progression. In this study, adipose-derived stem cells (ASCs) were engineered to produce exosomes (Ex) that target the TM4SF5 protein on tumors. Moreover, MACC1-targeting microRNA was encapsulated within the Ex, resulting in TM4SF5-targeting Ex (MACC1-suppressing miRNA; miR-143). The anticancer effects of these Ex were investigated in vitro using the human colorectal cell line HCT116 and in vivo using colorectal cancer mouse xenograft models. In the in vivo assessment, administration of TM4SF5-targeting Ex[miR-143], referred to as tEx[miR-143] herein, resulted in the smallest tumor size, the lowest tumor growth rate, and the lightest excised tumors compared to other treatments ( p < 0.05). It also led to the decreased expression of MACC-1 and anti-apoptotic markers MCL-1 and Bcl-xL while inducing the highest expression of pro-apoptotic markers BAX and BIM. These results were consistent with in vitro findings, where t Ex[miR-143] demonstrated the highest inhibition of HCT116 cell migration and invasion. These findings highlight the potential of tEx[miR-143] as an effective therapeutic strategy for colorectal cancer, demonstrating promising results in both targetability and anti-tumor effects in vitro and in vivo, warranting further investigation in clinical settings.
- Published
- 2024
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