Work

The METTL3/TRAP1 axis as a key regulator of 5-fluorouracil chemosensitivity in colorectal cancer

Year: 2024

Type: article

Abstract: 5-Fluorouracil (5-FU) stands as the frontline chemotherapeutic for colorectal cancer (CRC). However, the enduring challenge of chemoresistance to 5-FU persists in clinical practice, and the precise regulatory mechanisms governing 5-FU response and resistance in CRC remain elusive. This study aims to investigate the role and mechanisms of METTL3 in regulating 5-FU chemosensitivity in CRC cells. Practically, 5-FU treatment not only hindered cell viability and induced apoptosis but also led to a reduction in METTL3 expression in HCT-116 and HCT-8 cells. Through a range of assays including drug sensitivity, EdU, colony formation, TUNEL staining, and flow cytometry, we unveiled that METTL3 depletion heightened 5-FU sensitivity and augmented apoptosis induction in vitro and in vivo. Conversely, METTL3 overexpression conferred HCT-116 and HCT-8 cells with resistance to 5-FU. Mechanistically, METTL3 regulates 5-FU sensitivity and apoptosis induction by modulating TRAP1 expression. Further, m6A colorimetric ELISA and MeRIP-qPCR assays demonstrated that METTL3 regulated TRAP1 expression in an m6A-dependent manner. Furthermore, the overexpression of TRAP1 mitigated the cytotoxic effects of 5-FU on HCT-116 and HCT-8 cells. In conclusion, this study uncovers the pivotal role of the METTL3/TRAP1 axis in modulating 5-FU chemosensitivity in CRC.

Source: Molecular and Cellular Biochemistry

DOI: 10.1007/s11010-024-05116-8

Authors: Qingjie Kang, Xiaoyu Hu, Zhenzhou Chen, Xiaolong Liang, Song Xiang, Ziwei Wang

Institutions: The Affiliated Yongchuan Hospital of Chongqing Medical University, Chongqing Medical University

Language: English

Topic: RNA modifications and cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,890