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On-line Access: 2022-06-16

Received: 2021-11-28

Revision Accepted: 2022-05-15

Crosschecked: 2022-09-16

Cited: 0

Clicked: 198

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Jianying ZHANG

https://orcid.org/0000-0003-2938-9526

Jintao ZHANG

https://orcid.org/0000-0001-8879-0286

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Journal of Zhejiang University SCIENCE B 2022 Vol.23 No.9 P.760-769

http://doi.org/10.1631/jzus.B2100985


BCAT1 promotes lung adenocarcinoma progression through enhanced mitochondrial function and NF-κB pathway activation


Author(s):  Mengdan YU, Qianwei ZHAO, Jinxia LI, Fang XU, Zhibiao ZHANG, Yixian LIU, Liping DAI, Bingxia ZHANG, Jianying ZHANG, Jintao ZHANG

Affiliation(s):  Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450052, China; more

Corresponding email(s):   jtzhang@zzu.edu.cn, jianyingzhang@hotmail.com

Key Words:  BCAT1, LUAD, Mitochondrial function, ROS, NF-κB pathway


Mengdan YU, Qianwei ZHAO, Jinxia LI, Fang XU, Zhibiao ZHANG, Yixian LIU, Liping DAI, Bingxia ZHANG, Jianying ZHANG, Jintao ZHANG. BCAT1 promotes lung adenocarcinoma progression through enhanced mitochondrial function and NF-κB pathway activation[J]. Journal of Zhejiang University Science B, 2022, 23(9): 760-769.

@article{title="BCAT1 promotes lung adenocarcinoma progression through enhanced mitochondrial function and NF-κB pathway activation",
author="Mengdan YU, Qianwei ZHAO, Jinxia LI, Fang XU, Zhibiao ZHANG, Yixian LIU, Liping DAI, Bingxia ZHANG, Jianying ZHANG, Jintao ZHANG",
journal="Journal of Zhejiang University Science B",
volume="23",
number="9",
pages="760-769",
year="2022",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2100985"
}

%0 Journal Article
%T BCAT1 promotes lung adenocarcinoma progression through enhanced mitochondrial function and NF-κB pathway activation
%A Mengdan YU
%A Qianwei ZHAO
%A Jinxia LI
%A Fang XU
%A Zhibiao ZHANG
%A Yixian LIU
%A Liping DAI
%A Bingxia ZHANG
%A Jianying ZHANG
%A Jintao ZHANG
%J Journal of Zhejiang University SCIENCE B
%V 23
%N 9
%P 760-769
%@ 1673-1581
%D 2022
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2100985

TY - JOUR
T1 - BCAT1 promotes lung adenocarcinoma progression through enhanced mitochondrial function and NF-κB pathway activation
A1 - Mengdan YU
A1 - Qianwei ZHAO
A1 - Jinxia LI
A1 - Fang XU
A1 - Zhibiao ZHANG
A1 - Yixian LIU
A1 - Liping DAI
A1 - Bingxia ZHANG
A1 - Jianying ZHANG
A1 - Jintao ZHANG
J0 - Journal of Zhejiang University Science B
VL - 23
IS - 9
SP - 760
EP - 769
%@ 1673-1581
Y1 - 2022
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2100985


Abstract: 
Lung cancer is one of the most prevalent and malignant cancers, among which lung adenocarcinoma (LUAD) accounts for the majority and remains a major cause of cancer-related mortality worldwide (Cui et al., 2019). Despite the growing intensity of research on the pathobiology and progression of lung cancer and the fact that many genes have been identified as potential drivers and targets for therapy (Luo et al., 2019; Zhang et al., 2019), the treatment and prognosis of lung cancer patients have hardly improved. Therefore, this study aimed to investigate the precise mechanism of lung cancer development and explore efficient diagnostic and therapeutic methods for clinical treatment.

BCAT1通过增强线粒体功能并激活NF-κB通路促进肺腺癌发展

余蒙丹1,2*,赵倩伟1*,李金霞2,许芳1,章智彪3,刘懿贤1,代丽萍1,4,张丙霞3,张建营1,4,章金涛1,4
1郑州大学河南省医药科学研究院,中国郑州市,450052
2郑州大学医学科学院基础医学院,中国郑州市,450052
3郑州大学生命科学学院,中国郑州市,450001
4郑州大学河南省肿瘤流行病学重点实验室,食管癌防治国家重点实验室,中国郑州市,450052
目的:探究BCAT1在肺腺癌发展过程中的生物学作用及其分子机制。
创新点:首次证实BCAT1通过调控线粒体功能和NF-κB通路影响肺腺癌发展,为肺腺癌发展的分子机制研究和临床治疗提供了新见解。
方法:首先通过免疫组化确定BCAT1蛋白在临床肺腺癌患者癌与癌旁组织中的表达,然后采用慢病毒侵染法构建BCAT1过表达或敲低的A549稳转株并进行增殖、迁移和侵袭实验。此外分别通过裸鼠皮下成瘤实验研究BCAT1对肺腺癌体内成瘤与肿瘤生长能力的影响;通过CCK8、qRT-PCR、活性氧与氧消耗率检测等实验研究BCAT1对支链氨基酸代谢和线粒体功能的影响。最后经转录组学与蛋白质免疫印迹(western blot)筛选并确定BCAT1影响肺腺癌发展的信号通路。
结论:BCAT1蛋白在肺腺癌患者的肺癌组织中呈过高表达状态,且BCAT1可增强肺腺癌细胞在体外与体内的增殖与迁移侵袭能力。BCAT1蛋白可能通过增强肺腺癌细胞中支链氨基酸代谢、线粒体生物合成和呼吸作用,降低胞内ROS含量,下调NFKBIB转录水平并激活NF-κB通路,促进肺腺癌发展。

关键词:BCAT1;肺腺癌;线粒体功能;活性氧;NF-κB

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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