Expression of GPSM1 in lung adenocarcinoma and its regulation and potential mechanism of glycolysis in lung adenocarcinoma cells

CHENG Jinfeng; JIANG Wanli

doi:10.14188/j.1671-8852.2024.0440

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Expression of GPSM1 in lung adenocarcinoma and its regulation and potential mechanism of glycolysis in lung adenocarcinoma cells

更新时间：2026-11-05

- Expression of GPSM1 in lung adenocarcinoma and its regulation and potential mechanism of glycolysis in lung adenocarcinoma cells
- Medical Journal of Wuhan University Vol. 46, Issue 6, Pages: 729-737(2025)
- 作者机构：
  
  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
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0440
  CLC： R734.2
- Received：10 June 2024，
  
  Published：25 June 2025
- 稿件说明：
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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.

摘要

目的

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

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

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

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。

Abstract

Objective

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

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

The gene GPSM1 exhibits low expression in both lung adenocarcinoma tissues and cells (both

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

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.

关键词

Keywords

references

SUNG H , FERLAY J , SIEGEL R L , et al . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J ] . CA Cancer J Clin , 2021 , 71 ( 3 ): 209 ‑ 249 .

郑荣寿 , 张思维 , 孙可欣 , 等 . 2016年中国恶性肿瘤流行情况分析 [J ] . 中华肿瘤杂志 , 2023 , 45 ( 3 ): 212 ‑ 220 .

ZHENG R S , ZHANG S W , SUN K X , et al . Cancer statistics in China, 2016 [J ] . Chin J Oncol , 2023 , 45 ( 3 ): 212 ‑ 220 .

TAN A C , TAN D S W . Targeted therapies for lung cancer patients with oncogenic driver molecular alterations [J ] . J Clin Oncol , 2022 , 40 ( 6 ): 611 ‑ 625 .

SANADA K , TSAI L H . G protein betagamma subunits and AGS3 control spindle orientation and asymmetric cell fate of cerebral cortical progenitors [J ] . Cell , 2005 , 122 ( 1 ): 119 ‑ 131 .

GROVES B , GONG Q , XU Z , et al . A specific role of AGS3 in the surface expression of plasma membrane proteins [J ] . Proc Natl Acad Sci USA , 2007 , 104 ( 46 ): 1 8103‑ 18108 .

VURAL A , MCQUISTON T J , BLUMER J B , et al . Normal autophagic activity in macrophages from mice lacking Gαi3,AGS3,or RGS19 [J ] . PLoS One , 2013 , 8 ( 11 ): e81886 .

YAN J , ZHANG Y M , YU H R , et al . GPSM1 impairs metabolic homeostasis by controlling a pro‑inflammatory pathway in macrophages [J ] . Nat Commun , 2022 , 13 ( 1 ): 7260 .

ADEKOYA T O , SMITH N , ALADENIYI T , et al . Activator of G protein signaling 3 modulates prostate tumor development and progression [J ] . Carcinogenesis , 2019 , 40 ( 12 ): 1504 ‑ 1513 .

CHEN Y , SONG Y L , WANG L . G‑protein signaling modulator 1 promotes colorectal cancer metastasis by PI3K/AKT/mTOR signaling and autophagy [J ] . Int J Biochem Cell Biol , 2023 , 157 : 106388 .

ZHANG Y , ZHOU B , SUN J J , et al . Knockdown of GPSM1 inhibits the proliferation and promotes the apoptosis of B‑cell acute lymphoblastic leukemia cells by suppressing the ADCY6‑RAPGEF3‑JNK signaling pathway [J ] . Pathol Oncol Res , 2021 , 27 : 643376 .

SHI H , REN H R , YANG X J , et al . Overexpression of activator of G‑protein signaling 3 decreases the proliferation of esophageal squamous cell carcinoma [J ] . Pathol Res Pract , 2015 , 211 ( 6 ): 449 ‑ 455 .

STINE Z E , SCHUG Z T , SALVINO J M , et al . Targeting cancer metabolism in the era of precision oncology [J ] . Nat Rev Drug Discov , 2022 , 21 ( 2 ): 141 ‑ 162 .

BAO X T , ZHANG J H , HUANG G M , et al . The crosstalk between HIFs and mitochondrial dysfunctions in cancer development [J ] . Cell Death Dis , 2021 , 12 ( 2 ): 215 .

LING S B , SHAN Q N , ZHAN Q F , et al . USP22 promotes hypoxia‑induced hepatocellular carcinoma stemness by a HIF1α/USP22 positive feedback loop upon TP53 inactivation [J ] . Gut , 2020 , 69 ( 7 ): 1322 ‑ 1334 .

ZHOU F , SUN J G , YE L Y , et al . Fibronectin promotes tumor angiogenesis and progression of non‑small‑cell lung cancer by elevating WISP3 expression via FAK/MAPK/HIF‑1α axis and activating Wnt signaling pathway [J ] . Exp Hematol Oncol , 2023 , 12 ( 1 ): 61 .

KERR E M , GAUDE E , TURRELL F K , et al . Mutant Kras copy number defines metabolic reprogramming and therapeutic susceptibilities [J ] . Nature , 2016 , 531 ( 7592 ): 110 ‑ 113 .

SINGH J P , QIAN K , LEE J S , et al . O‑GlcNAcase targets pyruvate kinase M2 to regulate tumor growth [J ] . Oncogene , 2020 , 39 ( 3 ): 560 ‑ 573 .

GÓMEZ V , EYKYN T R , MUSTAPHA R , et al . Breast cancer‑associated macrophages promote tumorigenesis by suppressing succinate dehydrogenase in tumor cells [J ] . Sci Signal , 2020 , 13 ( 652 ): eaax4585 .

LIU J , ZHANG X M , CHEN K , et al . CCR7 chemokine receptor‑Inducible lnc‑Dpf3 restrains dendritic cell migration by inhibiting HIF‑1α‑Mediated glycolysis [J ] . Immunity , 2019 , 50 ( 3 ): 600 ‑ 615.e15 .

ZHENG F , CHEN J N , ZHANG X Q , et al . The HIF‑1α antisense long non‑coding RNA drives a positive feedback loop of HIF‑1α mediated transactivation and glycolysis [J ] . Nat Commun , 2021 , 12 ( 1 ): 1341 .

COWMAN S J , KOH M Y . Revisiting the HIF switch in the tumor and its immune microenvironment [J ] . Trends Cancer , 2022 , 8 ( 1 ): 28 ‑ 42 .

LI H X , LIANG J H , WANG J , et al . Mex3a promotes oncogenesis through the RAP1/MAPK signaling pathway in colorectal cancer and is inhibited by hsa‑miR‑6887‑3p [J ] . Cancer Commun (Lond) , 2021 , 41 ( 6 ): 472 ‑ 491 .

MA Q X , JIANG H F , MA L N , et al . The moonlighting function of glycolytic enzyme enolase‑1 promotes choline phospholipid metabolism and tumor cell proliferation [J ] . Proc Natl Acad Sci USA , 2023 , 120 ( 15 ): e2209435120 .

PARK J S , BURCKHARDT C J , LAZCANO R , et al . Mechanical regulation of glycolysis via cytoskeleton architecture [J ] . Nature , 2020 , 578 ( 7796 ): 621 ‑ 626 .

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