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<p>Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy associated with poor clinical outcomes. RHOBTB2, an atypical member of the Rho-GTPase family, contains a conserved GTPase domain at its N-terminus. While previous studies have implicated RHOBTB2 in AML progression, its underlying mechanisms remain inadequately defined. In this study, bioinformatics analyses revealed that RHOBTB2 is markedly upregulated in AML and correlates with unfavorable prognosis. To elucidate its functional role, we overexpressed or silenced RHOBTB2 in human AML cell lines KG-1 and MOLM-13. Functional assays, including CCK-8, Transwell, and Annexin V/PI staining, demonstrated that RHOBTB2 overexpression enhanced proliferation and migration, suppressed apoptosis, and shortened G0/G1 phase. Conversely, RHOBTB2 silencing exerted opposing effects. In addition, a direct interaction between RHOBTB2 and KLHL13 was identified through STRING database predictions and validated by co-immunoprecipitation. Western blot analysis confirmed that RHOBTB2 upregulates KLHL13 protein expression levels. Notably, KLHL13 downregulation induced by RHOBTB2 knockdown was reversed upon treatment with the proteasome inhibitor MG132, indicating that RHOBTB2 stabilizes KLHL13 by inhibiting its proteasomal degradation. Collectively, our findings highlight the RHOBTB2/KLHL13/Hippo pathway as a critical regulatory mechanism in AML malignancy and suggest RHOBTB2 as a potential therapeutic target.</p>

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RHOBTB2 enhances cell proliferation of acute myeloid leukemia by modulating Hippo-YAP1 signaling and dependent of KLHL13

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月17日

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  • Yao Liu,
  • Fanghui Zhou,
  • Lianjie Wang,
  • Yanming Xue,
  • Wei Wang

摘要

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy associated with poor clinical outcomes. RHOBTB2, an atypical member of the Rho-GTPase family, contains a conserved GTPase domain at its N-terminus. While previous studies have implicated RHOBTB2 in AML progression, its underlying mechanisms remain inadequately defined. In this study, bioinformatics analyses revealed that RHOBTB2 is markedly upregulated in AML and correlates with unfavorable prognosis. To elucidate its functional role, we overexpressed or silenced RHOBTB2 in human AML cell lines KG-1 and MOLM-13. Functional assays, including CCK-8, Transwell, and Annexin V/PI staining, demonstrated that RHOBTB2 overexpression enhanced proliferation and migration, suppressed apoptosis, and shortened G0/G1 phase. Conversely, RHOBTB2 silencing exerted opposing effects. In addition, a direct interaction between RHOBTB2 and KLHL13 was identified through STRING database predictions and validated by co-immunoprecipitation. Western blot analysis confirmed that RHOBTB2 upregulates KLHL13 protein expression levels. Notably, KLHL13 downregulation induced by RHOBTB2 knockdown was reversed upon treatment with the proteasome inhibitor MG132, indicating that RHOBTB2 stabilizes KLHL13 by inhibiting its proteasomal degradation. Collectively, our findings highlight the RHOBTB2/KLHL13/Hippo pathway as a critical regulatory mechanism in AML malignancy and suggest RHOBTB2 as a potential therapeutic target.