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

Autor: Ying, Zhu, Zhirui, Liu, Yiqi, Wan, Liping, Zou, Liping, Liu, Shuangjin, Ding, Chen, Lu, Fang, Qiu
Rok vydání: 2022
Předmět:
Zdroj: Clinical Immunology. 242:109094
ISSN: 1521-6616
DOI: 10.1016/j.clim.2022.109094
Popis: 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.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.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.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.
Databáze: OpenAIRE