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<p>Diffuse large B-cell lymphoma (DLBCL) is commonly treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), but up to 40% of patients have refractory or relapsing disease and show unsatisfactory responses to salvage treatment. Heat shock factor 1 (HSF1) regulates the transcription of a group of oncogenes, promoting chemoresistance and representing a promising therapeutic target. However, the role and mechanism of HSF1 in DLBCL remain unknown. In this study, we discovered that the overexpression of HSF1 was correlated with unfavorable treatment response and poor prognosis in patients with DLBCL. Inhibition of HSF1 via shRNA or DTHIB, a pharmacological inhibitor of HSF1, inhibited cell proliferation and increased chemosensitivity to vincristine and doxorubicin both in vitro and in vivo. Mechanistically, we revealed that genes related to the cell cycle, DNA repair, and p53 signalling pathways, including CCNB1, CCNE2, E2F2, and XRCC2, were directly regulated by HSF1 in a protein arginine methyltransferase 5 (PRMT5) -dependent manner. These findings demonstrated that the significant transcriptional regulator HSF1 promoted cell proliferation and chemoresistance in DLBCL. Targeting HSF1 may serve as a promising therapeutic strategy that enhances the antitumor effects of chemotherapy in DLBCL.</p>

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Heat shock factor 1 promotes proliferation and chemoresistance in diffuse large B-cell lymphoma by enhancing the cell cycle and DNA repair

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月17日

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  • Yu Fang,
  • Liang Cheng,
  • Ming Huang,
  • Yi Cao,
  • Qihua Zou,
  • Jun Cai,
  • Yuchen Zhang,
  • Yi Xia,
  • Huiqiang Huang,
  • Xu Chen,
  • Qingqing Cai

摘要

Diffuse large B-cell lymphoma (DLBCL) is commonly treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), but up to 40% of patients have refractory or relapsing disease and show unsatisfactory responses to salvage treatment. Heat shock factor 1 (HSF1) regulates the transcription of a group of oncogenes, promoting chemoresistance and representing a promising therapeutic target. However, the role and mechanism of HSF1 in DLBCL remain unknown. In this study, we discovered that the overexpression of HSF1 was correlated with unfavorable treatment response and poor prognosis in patients with DLBCL. Inhibition of HSF1 via shRNA or DTHIB, a pharmacological inhibitor of HSF1, inhibited cell proliferation and increased chemosensitivity to vincristine and doxorubicin both in vitro and in vivo. Mechanistically, we revealed that genes related to the cell cycle, DNA repair, and p53 signalling pathways, including CCNB1, CCNE2, E2F2, and XRCC2, were directly regulated by HSF1 in a protein arginine methyltransferase 5 (PRMT5) -dependent manner. These findings demonstrated that the significant transcriptional regulator HSF1 promoted cell proliferation and chemoresistance in DLBCL. Targeting HSF1 may serve as a promising therapeutic strategy that enhances the antitumor effects of chemotherapy in DLBCL.