NDUFA4 promotes cell proliferation by enhancing oxidative phosphorylation in pancreatic adenocarcinoma.

IF 2.9 4区 生物学 Q2 BIOPHYSICS
Yue Zhang, Mengchen Ge, Yuxiang Chen, Yan Yang, Weibo Chen, Di Wu, Huihua Cai, Xuemin Chen, Xinquan Wu
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引用次数: 2

Abstract

Pancreatic adenocarcinoma (PAAD) is the third leading cause of cancer-related deaths, with a 5-year relative survival rate of 6%. Hence, novel therapeutic targets need to be urgently explored for PAAD. Recently, oxidative phosphorylation (OXPHOS) has been identified to contribute to the development of PAAD. Nicotinamide adenine dinucleotide + hydrogen (NADH) dehydrogenase (ubiquinone) 1 alpha subcomplex 4 (NDUFA4) is known to affect the mitochondrial respiration pathway. However, the function of NDUFA4 in PAAD remains unclear. In this study, NDUFA4 expression was examined in samples from patients with PAAD using real-time polymerase chain reaction and immunohistochemical staining. Furthermore, cell proliferation and cell cycle were analyzed using Cell Counting Kit-8 assay and flow cytometry. A xenograft tumor model derived from a PAAD cell line was developed to validate the in vitro findings. NDUFA4 was observed to be upregulated in the PAAD samples, and high levels were associated with a poor survival rate. NDUFA4 knockdown reduced cell proliferation by inducing G1 arrest in SW1990 cells. Mechanistically, NDUFA4 knockdown decreased the oxygen consumption rate, cellular adenosine triphosphate level, mitochondrial complex IV activity, and protein levels of COX6C and COX5B, which indicated the suppression of OXPHOS. In contrast, NDUFA4 overexpression exerted the opposite effects. Finally, NDUFA4 knockdown significantly inhibited the growth of the xenograft tumor derived from the SW1990 cell line in vivo. Therefore, NDUFA4 contributes to PAAD proliferation by enhancing OXPHOS.

Abstract Image

NDUFA4 通过增强胰腺腺癌的氧化磷酸化促进细胞增殖。
胰腺腺癌(PAAD)是导致癌症相关死亡的第三大原因,5 年相对生存率仅为 6%。因此,亟需探索治疗 PAAD 的新靶点。最近,氧化磷酸化(OXPHOS)被认为是 PAAD 的发病原因之一。众所周知,烟酰胺腺嘌呤二核苷酸+氢(NADH)脱氢酶(泛醌)1α亚复合物4(NDUFA4)会影响线粒体呼吸途径。然而,NDUFA4 在 PAAD 中的功能仍不清楚。本研究采用实时聚合酶链反应和免疫组化染色法检测了 PAAD 患者样本中 NDUFA4 的表达。此外,还使用细胞计数试剂盒-8测定法和流式细胞术分析了细胞增殖和细胞周期。为了验证体外研究结果,研究人员建立了一个源自 PAAD 细胞系的异种移植肿瘤模型。在 PAAD 样本中观察到 NDUFA4 上调,高水平与存活率低有关。敲除 NDUFA4 可诱导 SW1990 细胞 G1 停滞,从而减少细胞增殖。从机理上讲,NDUFA4敲除降低了氧消耗率、细胞三磷酸腺苷水平、线粒体复合体IV活性以及COX6C和COX5B的蛋白水平,这表明OXPHOS受到了抑制。相反,NDUFA4 的过表达则产生了相反的效果。最后,敲除 NDUFA4 能显著抑制 SW1990 细胞系异种移植瘤在体内的生长。因此,NDUFA4通过增强OXPHOS促进了PAAD的增殖。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
6.00
自引率
0.00%
发文量
22
审稿时长
6-12 weeks
期刊介绍: The Journal of Bioenergetics and Biomembranes is an international journal devoted to the publication of original research that contributes to fundamental knowledge in the areas of bioenergetics, biomembranes, and transport, including oxidative phosphorylation, photosynthesis, muscle contraction, as well as cellular and systemic metabolism. The timely research in this international journal benefits biophysicists, membrane biologists, cell biologists, biochemists, molecular biologists, physiologists, endocrinologists, and bio-organic chemists.
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