Impacts of TP53TG1 in cancer-associated fibroblasts-derived exosomes on epithelial-mesenchymal transition capacity of colorectal carcinoma cells by targeting miR-330-3p

Yawei Liu; Youwei Wang; Zhijuan Yu; Ziheng Wang

doi:10.1016/j.heliyon.2024.e30301

Impacts of TP53TG1 in cancer-associated fibroblasts-derived exosomes on epithelial-mesenchymal transition capacity of colorectal carcinoma cells by targeting miR-330-3p

Heliyon. 2024 Apr 26;10(9):e30301. doi: 10.1016/j.heliyon.2024.e30301. eCollection 2024 May 15.

Authors

Yawei Liu¹, Youwei Wang², Zhijuan Yu³, Ziheng Wang^{4

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Affiliations

¹ Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.
² Bengbu Medical College, Bengbu, Anhui, 233030, China.
³ Hubei University of Science and Technology, Xianning, Hubei, 437000, China.
⁴ Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China.
⁵ Suzhou Industrial Park Monash Research Institute of Science and Technology, Suzhou, Jiangsu, 215000, China.
⁶ The School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

Abstract

Objective: This research aims at clarifying the action and mechanisms of action of TP53TG1 in cancer-associated fibroblasts (CAF)-derived exosomes (EXs) on colorectal carcinoma (CRC) cells.

Methods: CAF and CAF-EXs isolated from CRC tissues were incubated with CRC SW480 cells to determine alterations in biological behavior, epithelial-mesenchymal transition (EMT) capacity, and TP53TG1 and miR-330-3p expression. In addition, a dual luciferase reporter (DLR) assay was conducted to verify the connection between TP53TG1 and miR-330-3p, and the impacts of the two genes on CRC cells were analyzed.

Results: CRC-CAF-EXs extracted from CRC tissues were successfully identified and were able to promote SW480 multiplication, invasiveness, migration, and EMT ability while inhibiting apoptosis (P < 0.05). In addition, TP53TG1 increased and miR-330-3p decreased in SW480 when cultured with CRC-CAF-EXs (P < 0.05). The DLR assay identified notably reduced fluorescence activity of TP53TG1-WT after transfection with miR-330-3p-mimics (P < 0.05). Furthermore, SW480 cell multiplication, invasiveness and migration were found to be enhanced and the apoptosis decreased after up-regulating TP53TG1, while suppressing TP53TG1 and up-regulating miR-330-3p contributed to quite the opposite effect (P < 0.05). Moreover, by elevating TP53TG1 and miR-330-3p simultaneously, we found a cell activity similar to the NC group (P > 0.05).

Conclusion: By targeting miR-330-3p, TP53TG1 in CRC-CAF-EXs can enhance CRC cell activity and EMT capacity and inhibit apoptosis.

Keywords: Cancer-associated fibroblasts; Colorectal carcinoma; Epithelial-mesenchymal transition; Exosomes; TP53TG1; miR-330-3p.