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Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Hydrogen gas inhibits lung cancer progression through targeting SMC3
Dongchang Wang1, Lifei Wang1, Yu Zhang1
1Department of Respiration, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Abstract:
Lung cancer is one of the most common lethal malignancies in the globe. The patients' prognoses are dim due to its high metastatic potential and drug resistance. Therefore, in the present study, we aim to find a more potent therapeutic approach for lung cancer. We mainly explored the function of hydrogen gas (H2) on cell viability, apoptosis, migration and invasion in lung cancer cell lines A549 and H1975 by CCK-8, flow cytometry, wound healing and transwell assays, respectively. We used RNA-seq, qPCR and western blotting to detect the different expression genes (DEGs) between H2 group and control group to find the gene related to chromosome condensation. Besides, we confirmed the structural maintenance of chromosomes 3 (SMC3) and H2 on the progression of lung cancer in vitro and vivo. Results showed that H2 inhibited cell viability, migration and invasion, and catalyzed cell apoptosis and H2 induced A549 and H1975 cells G2/M arrest. Besides, H2 down-regulated the expression of NIBPL, SMC3, SMC5 and SMC6, and also reduced the expression of Cyclin D1, CDK4 and CDK6. H2 translocated the subcellular location of SMC3 during cell division and decreased its stability and increased its ubiquitination in both A549 and H1975 cells. In addition, inhibition of the proliferation, migration and invasion and promotion of the apoptosis of A549 and H1975 cells induced by H2 were all abolished when overexpressed SMC3 in the presence of H2. Animal experimental assay demonstrated that the tumor weight in H2 group was significantly smaller than that in control group, but was bigger than cis-platinum group. The expression of Ki-67, VEGF and SMC3 were decreased when mice were treated with H2 or cis-platinum, especially for cis-platinum. All data suggested that H2 inhibited lung cancer progression through down-regulating SMC3, a regulator for chromosome condensation, which provided a new method for the treatment of lung cancer.
Insights
Hydrogen gas (H2) effectively inhibits lung cancer progression by down-regulating structural maintenance of chromosomes 3 (SMC3), a key regulator of chromosome condensation. This offers a promising new therapeutic strategy for lung cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Gas Therapy
Background:
- Lung cancer remains a leading cause of cancer-related deaths globally.
- High metastatic potential and drug resistance contribute to poor patient prognoses.
- Novel therapeutic strategies are urgently needed to improve lung cancer treatment outcomes.
Purpose of the Study:
- To investigate the therapeutic potential of hydrogen gas (H2) in lung cancer.
- To elucidate the molecular mechanisms underlying H2's effects on lung cancer cells.
- To evaluate the role of structural maintenance of chromosomes 3 (SMC3) in H2-mediated anti-cancer effects.
Main Methods:
- Cell viability, apoptosis, migration, and invasion assays (CCK-8, flow cytometry, wound healing, Transwell).
- RNA sequencing (RNA-seq), quantitative PCR (qPCR), and Western blotting to identify differentially expressed genes.
- In vitro and in vivo experiments using lung cancer cell lines (A549, H1975) and a mouse xenograft model.
Main Results:
- H2 significantly inhibited lung cancer cell viability, migration, and invasion while promoting apoptosis and G2/M cell cycle arrest.
- H2 downregulated key genes including NIBPL, SMC3, SMC5, SMC6, Cyclin D1, CDK4, and CDK6.
- H2 treatment disrupted SMC3 subcellular localization, decreased its stability, and increased its ubiquitination, effects reversed by SMC3 overexpression.
Conclusions:
- H2 inhibits lung cancer progression by down-regulating SMC3, a regulator of chromosome condensation.
- SMC3 plays a critical role in H2-mediated inhibition of proliferation, migration, and invasion, and promotion of apoptosis.
- H2 represents a potential novel therapeutic agent for lung cancer treatment.
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