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.

Autor: Choi BJ; Department of Surgery, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon 34943, Republic of Korea.; Catholic Central Laboratory of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea., Lee D; Catholic Central Laboratory of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.; Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea., Park JH; Catholic Central Laboratory of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.; Department of Surgery, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Republic of Korea., Hong TH; Catholic Central Laboratory of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.; Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea., Kim OH; Catholic Central Laboratory of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.; Translational Research Team, Surginex Co., Ltd., Seoul 06591, Republic of Korea., Lee SC; Department of Surgery, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon 34943, Republic of Korea., Kim KH; Catholic Central Laboratory of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.; Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Gyeonggi 11765, Republic of Korea., Choi HJ; Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea., Kim SJ; Catholic Central Laboratory of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.; Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea.; Translational Research Team, Surginex Co., Ltd., Seoul 06591, Republic of Korea.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Aug 26; Vol. 25 (17). Date of Electronic Publication: 2024 Aug 26.
DOI: 10.3390/ijms25179232
Abstrakt: 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.
Databáze: MEDLINE
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