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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1384141

FTO Diversely Influences Sensitivity of Neuroblastoma Cells to Various Chemotherapeutic Drugs

Provisionally accepted
Meizhen Lin Meizhen Lin 1,2Zhongyan Hua Zhongyan Hua 1,2*Zhijie Li Zhijie Li 1,2*
  • 1 Department of Pediatrics, ShengJing Hospital of China Medical University, Shenyang, Liaoning Province, China
  • 2 Liaoning Key Laboratory of Research and Application of Animal Models for Environmental and Metabolic Diseases, Sheng Jing Hospital Affiliated, China Medical University, Shengyang, China

The final, formatted version of the article will be published soon.

    Chemotherapy resistance is a significant factor in treatment failure in patients with neuroblastoma (NB), and directly affect patient prognosis. Therefore, identifying novel therapeutic targets to enhance chemosensitivity is essential to improve the cure rate and prognosis of patients with NB. In this study, we investigated the role of FTO in chemosensitivity of NB cells to various chemotherapeutic drugs. Our results showed that high FTO expression was positively correlated with increased survival probability and favorable prognostic factors in patients with NB. FTO overexpression inhibited cell proliferation, whereas FTO knockdown promoted cell proliferation in NB cells. FTO expression alteration had contrasting effects on NB cells sensitivity to etoposide but had no significant impact on sensitivity to cisplatin. Downregulation of FTO reduced the sensitivity of NB cells to paclitaxel, whereas upregulation of FTO enhanced its sensitivity. Additionally, the sensitivities between patients with lower and higher FTO expression to various chemotherapeutic drugs or small-molecule inhibitors were different. Thus, FTO affects the sensitivities of NB cells differently depending on the different chemotherapeutic drugs and small-molecule inhibitors. This finding may guide physicians and patients choose the appropriate chemotherapeutic drugs or smallmolecule inhibitors for treatment. Chemoresistance is a leading cause of treatment failure, highlighting the need to explore new therapeutic targets and strategies for patients with NB(Q. Li et al., 2023).The fat mass and obesity-associated (FTO) gene is a nuclear protein of the AlkB related non-haem iron and 2-oxoglutarate-dependent oxygenase superfamily, playing a role in regulating energy metabolism, fat formation, cell differentiation, neurodevelopment, and tumor progression. Particularly, it plays an important role in various types of cancers(Y.

    Keywords: Neuroblastoma1, FTO2, chemotherapy sensitivity3, Paclitaxel4, etoposide5, cisplatin6

    Received: 08 Feb 2024; Accepted: 16 Aug 2024.

    Copyright: © 2024 Lin, Hua and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Zhongyan Hua, Department of Pediatrics, ShengJing Hospital of China Medical University, Shenyang, Liaoning Province, China
    Zhijie Li, Department of Pediatrics, ShengJing Hospital of China Medical University, Shenyang, Liaoning Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.