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Loss of NDUFS1 promotes gastric cancer progression by activating the mitochondrial ROS-HIF1α-FBLN5 signaling pathway.


ABSTRACT:

Background

Recent studies suggested that NDUFS1 has an important role in human cancers; however, the effects of NDUFS1 on gastric cancer (GC) are still not fully understood.

Methods

We confirmed that NDUFS1 is downregulated in GC cells through western blot immunohistochemistry and bioinformation analysis. The effect of NDUFS1 on GC was studied by CCK-8, colony formation, transwell assay in vitro and Mouse xenograft assay in vivo. Expression and subcellular localization of NDUFS1 and the content of mitochondrial reactive oxygen species (mROS) was observed by confocal reflectance microscopy.

Results

Reduced expression of NDUFS1 was found in GC tissues and cell lines. Also, NDUFS1 overexpression inhibited GC cell proliferation, migration, and invasion in vitro as well as growth and metastasis in vivo. Mechanistically, NDUFS1 reduction led to the activation of the mROS-hypoxia-inducible factor 1α (HIF1α) signaling pathway. We further clarified that NDUFS1 reduction upregulated the expression of fibulin 5 (FBLN5), a transcriptional target of HIF1α, through activation of mROS-HIF1α signaling in GC cells.

Conclusions

The results of this study indicate that NDUFS1 downregulation promotes GC progression by activating an mROS-HIF1α-FBLN5 signaling pathway.

SUBMITTER: Chen T 

PROVIDER: S-EPMC10575981 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Loss of NDUFS1 promotes gastric cancer progression by activating the mitochondrial ROS-HIF1α-FBLN5 signaling pathway.

Chen Tao T   Li Dongbao D   Wang Yunliang Y   Shen Xiaochun X   Dong Anqi A   Dong Chao C   Duan Kaipeng K   Ren Jiayu J   Li Weikang W   Shu Gege G   Yang Jiaoyang J   Xie Yufeng Y   Qian Fuliang F   Zhou Jin J  

British journal of cancer 20230829 8


<h4>Background</h4>Recent studies suggested that NDUFS1 has an important role in human cancers; however, the effects of NDUFS1 on gastric cancer (GC) are still not fully understood.<h4>Methods</h4>We confirmed that NDUFS1 is downregulated in GC cells through western blot immunohistochemistry and bioinformation analysis. The effect of NDUFS1 on GC was studied by CCK-8, colony formation, transwell assay in vitro and Mouse xenograft assay in vivo. Expression and subcellular localization of NDUFS1 a  ...[more]

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