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NADH脱氢酶亚基1/4/5通过介导特定的氧化磷酸化促进急性髓系白血病的存活。

NADH dehydrogenase subunit 1/4/5 promotes survival of acute myeloid leukemia by mediating specific oxidative phosphorylation.

作者信息

Kuang Ye, Peng Chuanmei, Dong Yulin, Wang Jia, Kong Fanbin, Yang Xiaoqing, Wang Yang, Gao Hui

机构信息

Department of Medical Laboratory, Yan'An Hospital, Kunming, Yunnan 650000, P.R. China.

出版信息

Mol Med Rep. 2022 Jun;25(6). doi: 10.3892/mmr.2022.12711. Epub 2022 Apr 15.

Abstract

Acute myeloid leukemia (AML) is a type of hematological malignancy caused by uncontrolled clonal proliferation of hematopoietic stem cells. The special energy metabolism mode of AML relying on oxidative phosphorylation is different from the traditional 'Warburg effect'. However, its mechanism is not clear. In the present study, it was demonstrated that the mRNA expression levels of NADH dehydrogenase subunit 1, 4 and 5 (ND1, ND4 and ND5) were upregulated in AML samples from The Cancer Genome Atlas database using the package in the R programming language. Reverse transcription‑quantitative PCR and ELISA were used to verify the upregulation of ND1, ND4 and ND5 in clinical samples. Pan‑cancer analysis revealed that the expression of ND1 was upregulated only in AML, ND2 was upregulated only in AML and thymoma, and ND4 was upregulated only in AML and kidney chromophobe. In the present study, it was demonstrated that silencing of ND1/4/5 could inhibit the proliferation of AML cells in transplanted tumor of nude mice. Additionally, it was found that oxidative phosphorylation and energy metabolism of AML cells were decreased after silencing of ND1/4/5. In conclusion, the present study suggested that ND1/4/5 may be involved in the regulation of oxidative phosphorylation metabolism in AML as a potential cancer‑promoting factor.

摘要

急性髓系白血病(AML)是一种由造血干细胞不受控制的克隆性增殖引起的血液系统恶性肿瘤。AML依赖氧化磷酸化的特殊能量代谢模式不同于传统的“瓦伯格效应”。然而,其机制尚不清楚。在本研究中,使用R编程语言中的软件包证明,来自癌症基因组图谱数据库的AML样本中NADH脱氢酶亚基1、4和5(ND1、ND4和ND5)的mRNA表达水平上调。采用逆转录定量PCR和ELISA法验证临床样本中ND1、ND4和ND5的上调。泛癌分析显示,ND1仅在AML中表达上调,ND2仅在AML和胸腺瘤中表达上调,ND4仅在AML和肾嫌色细胞癌中表达上调。在本研究中,证明沉默ND1/4/5可抑制裸鼠移植瘤中AML细胞的增殖。此外,发现沉默ND1/4/5后AML细胞的氧化磷酸化和能量代谢降低。总之,本研究表明,ND1/4/5可能作为一种潜在的促癌因子参与AML氧化磷酸化代谢的调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76a9/9052001/e55ec35ab502/mmr-25-06-12711-g00.jpg

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