1.黄冈市中心医院科教科 湖北 黄冈 438000
2.武汉大学人民医院胸外科 湖北 武汉 430060
程金凤,女,1979—,医学硕士,副主任护师,主要从事外科疾病的临床和基础研究,E‑mail:358437146@qq.com
江万里,男,1988—,医学博士,副主任医师,主要从事胸外科疾病的临床和基础研究,E‑mail:Jiang.wanli@qq.com
收稿:2024-06-10,
纸质出版:2025-06-25
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程金凤,江万里.GPSM1在肺腺癌中的表达及其对肺腺癌细胞糖酵解的调控与潜在机制[J].武汉大学学报(医学版),2025,46(06):729-737.
CHENG Jinfeng,JIANG Wanli.Expression of GPSM1 in lung adenocarcinoma and its regulation and potential mechanism of glycolysis in lung adenocarcinoma cells[J].Medical Journal of Wuhan University,2025,46(06):729-737.
程金凤,江万里.GPSM1在肺腺癌中的表达及其对肺腺癌细胞糖酵解的调控与潜在机制[J].武汉大学学报(医学版),2025,46(06):729-737. DOI: 10.14188/j.1671-8852.2024.0440.
CHENG Jinfeng,JIANG Wanli.Expression of GPSM1 in lung adenocarcinoma and its regulation and potential mechanism of glycolysis in lung adenocarcinoma cells[J].Medical Journal of Wuhan University,2025,46(06):729-737. DOI: 10.14188/j.1671-8852.2024.0440.
目的
2
探讨G蛋白信号调节受体1(GPSM1)在肺腺癌组织和细胞中的表达及其对肺腺癌细胞侵袭和迁移的影响与可能的机制。
方法
2
通过生物信息学方法分析TCGA数据库,探索GPSM1在肺腺癌组织与正常肺组织中的表达差异,并使用Western Blot法和qPCR法检测人正常肺支气管肺泡上皮细胞BEAS‑2B和人肺腺癌细胞A549、H1299、H460中GPSM1的表达水平,并选取GPSM1表达水平更低的H1299和H460细胞进行后续实验。构建GPSM1过表达质粒转染肺腺癌细胞,通过Transwell实验和细胞划痕实验分别检测过表达和敲低GPSM1对肺腺癌细胞侵袭和迁移的影响。使用LinkedOmics工具在线分析肺腺癌中GPSM1共表达基因并进行富集分析。通过检测糖酵解关键酶mRNA表达水平及细胞能量代谢分析明确GPSM1对肺腺癌细胞糖酵解的影响,并使用HIF‑1α激动剂探索GPSM1/HIF‑1α轴对肺腺癌细胞侵袭和迁移能力的影响。
结果
2
GPSM1在肺腺癌组织和细胞中均呈低表达。过表达GPSM1后,肺腺癌细胞侵袭和迁移能力显著降低;肺腺癌内GPSM1表达参与多种生物学过程;过表达GPSM1后,肺腺癌细胞糖酵解能力下降,且糖酵解本身不影响GPSM1表达水平;GPSM1过表达伴随肺腺癌细胞内HIF‑1α表达下调,且激活HIF‑1α后肺腺癌细胞迁移和侵袭能力得到恢复。
结论
2
GPSM1在肺腺癌组织和细胞中均呈低表达,其表达水平下调可能通过激活HIF‑1α/糖酵解通路促进肺腺癌细胞侵袭和迁移。
Objective
2
To investigate the expression of G‑protein signaling modulator 1 (GPSM1) in lung adenocarcinoma tissues and cells
and its impact on the invasion and migration of lung adenocarcinoma cells
along with potential mechanisms.
Methods
2
By analyzing the TCGA database through bioinformatics methods
we aimed to explore the differential expression of GPSM1 in lung adenocarcinoma tissues compared to normal lung tissues. Subsequently
we utilized Western Blot and qPCR techniques to measure the expression levels of GPSM1 in human normal bronchial epithelial cells (BEAS‑2B) and human lung adenocarcinoma cells (A549
H1299
and H460). Among these
H1299 and H460 cells with lower GPSM1 expression levels were selected for further experiments. Following this
we constructed a GPSM1 overexpression plasmid for transfection into lung adenocarcinoma cells and examined the impact of overexpressing or silencing GPSM1 on the invasive and migratory capabilities of lung adenocarcinoma cells using Transwell and wound healing assays
respectively. Additionally
we conducted an online analysis of co‑expressed genes of GPSM1 in lung adenocarcinoma and performed enrichment analysis using the LinkedOmics tool. Furthermore
through measuring the mRNA expression levels of key glycolysis enzymes and analyzing cellular energy metabolism
we elucidated the effect of GPSM1 on glycolysis in lung adenocarcinoma cells. Finally
we investigated the influence of the GPSM1/HIF‑1α axis on the invasive and migratory abilities of lung adenocarcinoma cells by using an activator of HIF‑1α.
Results
2
The gene GPSM1 exhibits low expression in both lung adenocarcinoma tissues and cells (both
P
<
0.01). Upon overexpression of GPSM1
the invasive and migratory abilities of lung adenocarcinoma cells significantly decrease. GPSM1 overexpression in lung adenocarcinoma is involved in multiple biological processes. Following GPSM1 overexpression
the glycolytic capacity of lung adenocarcinoma cells decreases
with glycolysis itself not affecting the expression levels of GPSM1. Overexpression of GPSM1 correlates with the downregulation of HIF‑1α expression in lung adenocarcinoma cells. Additionally
upon activation of HIF‑1α
the migratory and invasive capabilities of lung adenocarcinoma cells are restored.
Conclusion
2
The expression of GPSM1 is downregulated in both lung adenocarcinoma tissues and cells. This downregulation may promote invasion and migration of lung adenocarcinoma cells through activating the HIF‑1α/glycolysis pathway.
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