METTL3 antagonizes 5‑FU chemotherapy and confers drug resistance in colorectal carcinoma Corrigendum in /10.3892/ijo.2023.5549

Li,Min; Li,Min; Xia,Mingyue; Xia,Mingyue; Zhang,Ziyu; Zhang,Ziyu; Tan,Yanyin; Tan,Yanyin; Li,Enjie; Li,Enjie; Guo,Zhigang; Guo,Zhigang; Fang,Mingzhi; Fang,Mingzhi; Zhu,Yong; Zhu,Yong; Hu,Zhigang; Hu,Zhigang

doi:10.3892/ijo.2022.5396

METTL3 antagonizes 5‑FU chemotherapy and confers drug resistance in colorectal carcinoma

Corrigendum in: /10.3892/ijo.2023.5549

Authors:
- Min Li
- Mingyue Xia
- Ziyu Zhang
- Yanyin Tan
- Enjie Li
- Zhigang Guo
- Mingzhi Fang
- Yong Zhu
- Zhigang Hu
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Affiliations: Department of Oncology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China, Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu 210023, P.R. China, National Centre of Colorectal Disease, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
Published online on: July 19, 2022 https://doi.org/10.3892/ijo.2022.5396
Article Number: 106
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is one of top five leading causes of cancer‑associated mortalities worldwide. 5‑Fluorouracil (5‑FU) is the first‑line chemotherapeutic drug in the treatment of CRC; however, its antineoplastic efficiency is limited due to acquired drug resistance. The regulatory mechanism underlying 5‑FU chemotherapeutic response and drug resistance in CRC remains largely unknown. The present study identified that silencing of methyltransferase‑like 3 (METTL3) suppressed the proliferation and migration of CRC HCT‑8 cells. Using cell survival assays, flow cytometric and colony formation analyses, it was revealed that inhibition of METTL3 sensitized HCT‑8 cells to 5‑FU by enhancing DNA damage and inducing apoptosis in HCT‑8 cells under 5‑FU treatment. Furthermore, the expression of METTL3 was upregulated in 5‑FU‑resistant CRC cells (HCT‑8R), which contributed to drug resistance through regulation of RAD51 associated Protein 1 (RAD51AP1) expression. Western blotting, immunofluorescence staining and drug sensitivity assays demonstrated that knockdown of METTL3 augmented 5‑FU‑induced DNA damage and overcame 5‑FU‑resistance in HCT‑8R cells, which could be mimicked by inhibition of RAD51AP1. The present study revealed that the METTL3/RAD51AP1 axis plays an important role in the acquisition of 5‑FU resistance in CRC, and targeting METTL3/RAD51AP1 may be a promising adjuvant therapeutic strategy for patients with CRC, particularly for those with 5‑FU‑resistant CRC.

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