JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

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

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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,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2100985

@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",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/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
%P 760-769
%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/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
SP - 760
EP - 769
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
ER -
doi="https://doi.org/10.1631/jzus.B2100985"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

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。

关键词组：BCAT1；肺腺癌；线粒体功能；活性氧；NF-κB

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Reference

[1]AnanievaEA, WilkinsonAC, 2018. Branched-chain amino acid metabolism in cancer. Curr Opin Clin Nutr Metab Care, 21(1):64-70.

[2]ChenLP, LiQ, ZhengZW, et al., 2019. Design and optimize N-substituted EF24 as effective and low toxicity NF-‍κB inhibitor for lung cancer therapy via apoptosis-to-pyroptosis switch. Chem Biol Drug Des, 94(1):1368-1377.

[3]CuiYM, FangWF, LiCF, et al., 2019. Development and validation of a novel signature to predict overall survival in “driver gene-negative” lung adenocarcinoma (LUAD): results of a multicenter study. Clin Cancer Res, 25(5):1546-1556.

[4]FuSJ, LiZ, XiaoLB, et al., 2019. Glutamine synthetase promotes radiation resistance via facilitating nucleotide metabolism and subsequent DNA damage repair. Cell Rep, 28(5):1136-1143.E4.

[5]KoJH, OlonaA, PapathanassiuAE, et al., 2020. BCAT1 affects mitochondrial metabolism independently of leucine transamination in activated human macrophages. J Cell Sci, 133(22):jcs247957.

[6]LinXM, TanST, FuL, et al., 2020. BCAT1 overexpression promotes proliferation, invasion, and Wnt signaling in non-small cell lung cancers. Onco Targets Ther, 13:3583-3594.

[7]LoukiliN, Rosenblatt-VelinN, RolliJ, et al., 2010. Oxidants positively or negatively regulate nuclear factor κB in a context-dependent manner. J Biol Chem, 285(21):‍15746-15752.

[8]LuoJ, YaoY, JiSG, et al., 2019. PITX2 enhances progression of lung adenocarcinoma by transcriptionally regulating WNT3A and activating Wnt/β‍-catenin signaling pathway. Cancer Cell Int, 19:96.

[9]MorganMJ, LiuZG, 2011. Crosstalk of reactive oxygen species and NF-‍κB signaling. Cell Res, 21(1):103-115.

[10]OktyabriD, IshimuraA, TangeS, et al., 2016. DOT1L histone methyltransferase regulates the expression of BCAT1 and is involved in sphere formation and cell migration of breast cancer cell lines. Biochimie, 123:20-31.

[11]RaiAK, JaiswaN, MauryaCK, et al., 2019. Fructose-induced AGEs-RAGE signaling in skeletal muscle contributes to impairment of glucose homeostasis. J Nutr Biochem, 71:35-44.

[12]ShamekhiS, AbdolalizadehJ, OstadrahimiA, et al., 2020. Apoptotic effect of Saccharomyces cerevisiae on human colon cancer SW480 cells by regulation of Akt/NF-‍κB signaling pathway. Probiotics Antimicrob Proteins, 12(1):311-319.

[13]TyagiM, PatroBS, 2019. Salinomycin reduces growth, proliferation and metastasis of cisplatin resistant breast cancer cells via NF-‍κB deregulation. Toxicol in Vitro, 60:125-133.

[14]XuY, YuWM, YangTT, et al., 2018. Overexpression of BCAT1 is a prognostic marker in gastric cancer. Hum Pathol, 75:41-46.

[15]ZhangJQ, SunGY, MeiXD, et al., 2019. Elevated FAM83A expression predicts poorer clincal outcome in lung adenocarcinoma. Cancer Biomark, 26(3):367-373.

[16]ZhangJX, WangXL, VikashV, et al., 2016. ROS and ROS-mediated cellular signaling. Oxid Med Cell Longev, 2016:4350965.

[17]ZhangL, HanJQ, 2017. Branched-chain amino acid transaminase 1 (BCAT1) promotes the growth of breast cancer cells through improving mTOR-mediated mitochondrial biogenesis and function. Biochem Biophys Res Commun, 486(2):224-231.

[18]ZhouLS, DongCS, XuZM, et al., 2021. NEDD8-conjugating enzyme E2 UBE2F confers radiation resistance by protecting lung cancer cells from apoptosis. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 22(11):959-965.

[19]ZhuWJ, ShaoYQ, PengY, 2017. MicroRNA-218 inhibits tumor growth and increases chemosensitivity to CDDP treatment by targeting BCAT1 in prostate cancer. Mol Carcinog, 56(6):1570-1577.

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BCAT1通过增强线粒体功能并激活NF-κB通路促进肺腺癌发展

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