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Published on: May 10, 2024
Loss of NDUFS1 promotes gastric cancer progression by activating the mitochondrial ROS-HIF1α-FBLN5 signaling pathway
Tao Chen1, Dongbao Li1, Yunliang Wang1
1Department of General Surgery, the First Affiliated Hospital of Soochow University, 215006, Suzhou, China.
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.
Insights
NDUFS1 downregulation promotes gastric cancer (GC) progression. This occurs through activation of the mitochondrial reactive oxygen species (mROS)-hypoxia-inducible factor 1α (HIF1α)-fibulin 5 (FBLN5) pathway, driving cancer cell growth and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- NDUFS1's role in human cancers is recognized, but its specific impact on gastric cancer (GC) remains unclear.
- Gastric cancer (GC) is a significant global health concern with complex underlying molecular mechanisms.
Purpose of the Study:
- To investigate the role and mechanism of NDUFS1 in gastric cancer (GC) progression.
- To elucidate the signaling pathway involved in NDUFS1-mediated GC development.
Main Methods:
- Western blot, immunohistochemistry, and bioinformatics analysis to assess NDUFS1 expression in GC.
- In vitro (CCK-8, colony formation, Transwell assays) and in vivo (mouse xenograft) experiments to evaluate NDUFS1's functional impact.
- Confocal microscopy to observe NDUFS1 localization and mitochondrial reactive oxygen species (mROS) levels.
Main Results:
- NDUFS1 expression was significantly downregulated in GC tissues and cell lines.
- NDUFS1 overexpression suppressed GC cell proliferation, migration, invasion, and tumor growth in vivo.
- NDUFS1 reduction activated the mROS-hypoxia-inducible factor 1α (HIF1α) pathway, leading to increased fibulin 5 (FBLN5) expression.
Conclusions:
- NDUFS1 downregulation is a key driver of gastric cancer (GC) progression.
- The mROS-HIF1α-FBLN5 signaling pathway is critically involved in NDUFS1-mediated GC development.
- Targeting NDUFS1 or this pathway may offer therapeutic strategies for gastric cancer.
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