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Article Open Access

Inhibition of FBP1 expression by KMT5A through TWIST1 methylation is one of the mechanisms leading to chemoresistance in breast cancer

  • Authors:
    • Xue Peng
    • Lisi Ma
    • Xuan Chen
    • Fen Tang
    • Xiangyun Zong
  • View Affiliations / Copyright

    Affiliations: Department of Breast Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, P.R. China
    Copyright: © Peng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 110
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    Published online on: July 3, 2024
       https://doi.org/10.3892/or.2024.8769
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Abstract

Lysine methyltransferase 5A (KMT5A) is the sole mammalian enzyme known to catalyse the mono‑methylation of histone H4 lysine 20 and non‑histone proteins such as p53, which are involved in the occurrence and progression of numerous cancers. The present study aimed to determine the function of KMT5A in inducing docetaxel (DTX) resistance in patients with breast carcinoma by evaluating glucose metabolism and the underlying mechanism involved. The upregulation or downregulation of KMT5A‑related proteins was examined after KMT5A knockdown in breast cancer (BRCA) cells by Tandem Mass Tag proteomics. Through differential protein expression and pathway enrichment analysis, the upregulated key gluconeogenic enzyme fructose‑1,6‑bisphosphatase 1 (FBP1) was discovered. Loss of FBP1 expression is closely related to the development and prognosis of cancers. A dual‑luciferase reporter gene assay confirmed that KMT5A inhibited the expression of FBP1 and that overexpression of FBP1 could enhance the chemotherapeutic sensitivity to DTX through the suppression of KMT5A expression. The KMT5A inhibitor UNC0379 was used to verify that DTX resistance induced by KMT5A through the inhibition of FBP1 depended on the methylase activity of KMT5A. According to previous literature and interaction network structure, it was revealed that KMT5A acts on the transcription factor twist family BHLH transcription factor 1 (TWIST1). Then, it was verified that TWSIT1 promoted the expression of FBP1 by using a dual‑luciferase reporter gene experiment. KMT5A induces chemotherapy resistance in BRCA cells by promoting cell proliferation and glycolysis. After the knockdown of the KMT5A gene, the FBP1 related to glucose metabolism in BRCA was upregulated. KMT5A knockdown expression and FBP1 overexpression synergistically inhibit cell proliferation and block cells in the G2/M phase. KMT5A inhibits the expression of FBP1 by methylating TWIST1 and weakening its promotion of FBP1 transcription. In conclusion, KMT5A was shown to affect chemotherapy resistance by regulating the cell cycle and positively regulate glycolysis‑mediated chemotherapy resistance by inhibiting the transcription of FBP1 in collaboration with TWIST1. KMT5A may be a potential therapeutic target for chemotherapy resistance in BRCA.
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Copy and paste a formatted citation
Spandidos Publications style
Peng X, Ma L, Chen X, Tang F and Zong X: Inhibition of FBP1 expression by KMT5A through TWIST1 methylation is one of the mechanisms leading to chemoresistance in breast cancer. Oncol Rep 52: 110, 2024.
APA
Peng, X., Ma, L., Chen, X., Tang, F., & Zong, X. (2024). Inhibition of FBP1 expression by KMT5A through TWIST1 methylation is one of the mechanisms leading to chemoresistance in breast cancer. Oncology Reports, 52, 110. https://doi.org/10.3892/or.2024.8769
MLA
Peng, X., Ma, L., Chen, X., Tang, F., Zong, X."Inhibition of FBP1 expression by KMT5A through TWIST1 methylation is one of the mechanisms leading to chemoresistance in breast cancer". Oncology Reports 52.2 (2024): 110.
Chicago
Peng, X., Ma, L., Chen, X., Tang, F., Zong, X."Inhibition of FBP1 expression by KMT5A through TWIST1 methylation is one of the mechanisms leading to chemoresistance in breast cancer". Oncology Reports 52, no. 2 (2024): 110. https://doi.org/10.3892/or.2024.8769
Copy and paste a formatted citation
x
Spandidos Publications style
Peng X, Ma L, Chen X, Tang F and Zong X: Inhibition of FBP1 expression by KMT5A through TWIST1 methylation is one of the mechanisms leading to chemoresistance in breast cancer. Oncol Rep 52: 110, 2024.
APA
Peng, X., Ma, L., Chen, X., Tang, F., & Zong, X. (2024). Inhibition of FBP1 expression by KMT5A through TWIST1 methylation is one of the mechanisms leading to chemoresistance in breast cancer. Oncology Reports, 52, 110. https://doi.org/10.3892/or.2024.8769
MLA
Peng, X., Ma, L., Chen, X., Tang, F., Zong, X."Inhibition of FBP1 expression by KMT5A through TWIST1 methylation is one of the mechanisms leading to chemoresistance in breast cancer". Oncology Reports 52.2 (2024): 110.
Chicago
Peng, X., Ma, L., Chen, X., Tang, F., Zong, X."Inhibition of FBP1 expression by KMT5A through TWIST1 methylation is one of the mechanisms leading to chemoresistance in breast cancer". Oncology Reports 52, no. 2 (2024): 110. https://doi.org/10.3892/or.2024.8769
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