2. Academic Validation
  3. PARP14 promotes the growth and glycolysis of acute myeloid leukemia cells by regulating HIF-1α expression

PARP14 promotes the growth and glycolysis of acute myeloid leukemia cells by regulating HIF-1α expression

  • Clin Immunol. 2022 Sep;242:109094. doi: 10.1016/j.clim.2022.109094.
Ying Zhu 1,  Zhirui Liu 2,  Yiqi Wan 2,  Liping Zou 3,  Liping Liu 4,  Shuangjin Ding 5,  Chen Lu 6,  Fang Qiu 7
Affiliations

Affiliations

  • 1 Aging and Vascular Diseases, Human Aging Research Institute (HARI), School of Life Science, and Jiangxi Key Laboratory of Human Aging, Nanchang University, Nanchang, Jiangxi 341000, China; Department of Blood Transfusion, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, China.
  • 2 Aging and Vascular Diseases, Human Aging Research Institute (HARI), School of Life Science, and Jiangxi Key Laboratory of Human Aging, Nanchang University, Nanchang, Jiangxi 341000, China.
  • 3 Department of Blood Transfusion, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, China.
  • 4 Department of Hematology, First Affiliated Hospital of Gannan Medical University，Ganzhou, Jiangxi 341000, China.
  • 5 Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing 100871, China.
  • 6 Center of Precision Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, China. Electronic address: [email protected].
  • 7 Department of Blood Transfusion, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, China. Electronic address: [email protected].
PMID: 35944879 DOI: 10.1016/j.clim.2022.109094
Abstract

Objective: Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a poor prognosis. This study aimed to investigate the action of PARP14 in the growth and glycolysis of AML.

Methods: The clinical samples of AML patients were collected, and the expression of PARP14 was detected. AML cells were transfected with PARP14, HIF-1α or treated with NF-KB inhibitor (BAY11-7082) or PARP14 Inhibitor (RBN012759). Cell proliferation was detected by CCK-8 and colony formation assays, Apoptosis by flow cytometry, glucose consumption and lactate production by glucose and lactate kits, ECAR and OCR by XF96 bioenergy analyzer, and related protein levels by Western blot. A mouse xenograft tumor model was established to evaluate the effect of PARP14 on tumor formation.

Results: Significant upregulation of PARP14 expression was observed in AML. PARP14 promoted AML cell proliferation and glycolysis and inhibited Apoptosis, while PARP14 deficiency had the opposite effect. PARP14 promoted HIF-1α expression by activating NF-κB. HIF-1α silencing reversed the cancer-promoting effect of PARP14. In vivo results suggested that PARP14 promoted tumor formation.

Conclusion: PARP14 induces AML cell growth and glycolysis by activating NF-κB and promoting HIF-1α expression, which may suggest new insights into the pathogenesis of AML.

Keywords

Acute myeloid leukemia; Glycolysis; HIF-1α; NF-κB; PARP14; Proliferation.

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