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 ORCID:

Lin ZHANG

https://orcid.org/0000-0001-8567-0238

Dianshuai GAO

Dianshuai GAO, https://orcid.org/0000-0001-8567-0238

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Journal of Zhejiang University SCIENCE B

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Hypoxia-induced ROS aggravate tumor progression through HIF-1α-SERPINE1 signaling in glioblastoma


Author(s):  Lin ZHANG, Yuanyuan CAO, Xiaoxiao GUO, Xiaoyu WANG, Xiao HAN, Kouminin KANWORE, Xiaoliang HONG, Han ZHOU, Dianshuai GAO

Affiliation(s):  School of Nursing, Xuzhou Medical University, Xuzhou 221004, China; more

Corresponding email(s):  gds@xzhmu.edu.cn

Key Words:  Glioblastoma; Hypoxia; Reactive oxygen species (ROS); Hypoxia-inducible factor-1α (HIF-1α); Serine protease inhibitor family E member 1 (SERPINE1)


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Lin ZHANG, Yuanyuan CAO, Xiaoxiao GUO, Xiaoyu WANG, Xiao HAN, Kouminin KANWORE, Xiaoliang HONG, Han ZHOU, Dianshuai GAO. Hypoxia-induced ROS aggravate tumor progression through HIF-1α-SERPINE1 signaling in glioblastoma[J]. Journal of Zhejiang University Science B, 2023, 24(3): 32-49.

@article{title="Hypoxia-induced ROS aggravate tumor progression through HIF-1α-SERPINE1 signaling in glioblastoma",
author="Lin ZHANG, Yuanyuan CAO, Xiaoxiao GUO, Xiaoyu WANG, Xiao HAN, Kouminin KANWORE, Xiaoliang HONG, Han ZHOU, Dianshuai GAO",
journal="Journal of Zhejiang University Science B",
volume="24",
number="1",
pages="32-49",
year="2023",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2200269"
}

%0 Journal Article
%T Hypoxia-induced ROS aggravate tumor progression through HIF-1α-SERPINE1 signaling in glioblastoma
%A Lin ZHANG
%A Yuanyuan CAO
%A Xiaoxiao GUO
%A Xiaoyu WANG
%A Xiao HAN
%A Kouminin KANWORE
%A Xiaoliang HONG
%A Han ZHOU
%A Dianshuai GAO
%J Journal of Zhejiang University SCIENCE B
%V 24
%N 1
%P 32-49
%@ 1673-1581
%D 2023
%I Zhejiang University Press & Springer

TY - JOUR
T1 - Hypoxia-induced ROS aggravate tumor progression through HIF-1α-SERPINE1 signaling in glioblastoma
A1 - Lin ZHANG
A1 - Yuanyuan CAO
A1 - Xiaoxiao GUO
A1 - Xiaoyu WANG
A1 - Xiao HAN
A1 - Kouminin KANWORE
A1 - Xiaoliang HONG
A1 - Han ZHOU
A1 - Dianshuai GAO
J0 - Journal of Zhejiang University Science B
VL - 24
IS - 1
SP - 32
EP - 49
%@ 1673-1581
Y1 - 2023
PB - Zhejiang University Press & Springer
ER -


Abstract: 
Hypoxia, as an important hallmark of the tumor microenvironment, is a major cause of oxidative stress and plays a central role in various malignant tumors, including glioblastoma. Elevated reactive oxygen species (ROS) in a hypoxic microenvironment promote glioblastoma progression; however, the underlying mechanism has not been clarified. Herein, we found that hypoxia promoted ROS production, and the proliferation, migration, and invasion of glioblastoma cells, while this promotion was restrained by ROS scavengers N-acetyl-L-cysteine (NAC) and diphenyleneiodonium chloride (DPI). Hypoxia-induced ROS activated hypoxia-inducible factor-1α (HIF-1α) signaling, which enhanced cell migration and invasion by epithelial-mesenchymal transition (EMT). Furthermore, the induction of serine protease inhibitor family E member 1 (SERPINE1) was ROS-dependent under hypoxia, and HIF-1α mediated SERPINE1 increase induced by ROS via binding to the SERPINE1 promoter region, thereby facilitating glioblastoma migration and invasion. Taken together, our data revealed that hypoxia-induced ROS reinforce the hypoxic adaptation of glioblastoma by driving the HIF-1α-SERPINE1 signaling pathway, and that targeting ROS may be a promising therapeutic strategy for glioblastoma.

缺氧诱导的ROS通过HIF-1α-SERPINE1信号通路促进胶质母细胞瘤恶性进展

张琳1,2,曹媛媛2,3,郭肖肖2,4,王潇雨2,韩笑5,Kouminin KANWORE2,洪晓亮2,周晗2,高殿帅2
1徐州医科大学护理学院,中国徐州市,221004
2徐州医科大学神经生物学重点实验室,中国徐州市,221004
3泰州市中医院超声科,中国泰州市,225300
4南京医科大学康达学院基础学院,中国连云港市,222000
5南京医科大学第四临床学院,中国南京市,211166
概要:缺氧作为肿瘤微环境的重要特征,是氧化应激的主要原因,在肿瘤(包括胶质母细胞瘤)的恶性进展中发挥重要作用。缺氧微环境中高水平活性氧(ROS)促进胶质母细胞瘤进展的潜在机制尚不清楚。本研究发现缺氧促进了胶质母细胞瘤细胞增殖、迁移和侵袭以及ROS生成,而这种促进作用可被ROS清除剂N-乙酰半胱氨酸(NAC)和二苯基氯化碘盐(DPI)抑制。缺氧诱导的ROS可激活缺氧诱导因子-1α(HIF-1α)信号,通过上皮-间充质转化(EMT)增强细胞迁移和侵袭。此外,在缺氧条件下,HIF-1α可与丝氨酸蛋白酶抑制剂家族E成员1(SERPINE1)启动子区结合,ROS经HIF-1α上调SERPINE1表达,进而促进胶质母细胞瘤细胞迁移和侵袭。综上所述,本研究揭示了缺氧诱导的ROS通过驱动HIF-1α-SERPINE1信号促进胶质母细胞瘤的缺氧适应,靶向ROS可能成为胶质母细胞瘤治疗的一种有效策略。

关键词组:胶质母细胞瘤;缺氧;活性氧(ROS);缺氧诱导因子-1α(HIF-1α);丝氨酸蛋白酶抑制剂家族E成员1(SERPINE1)

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

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