Hypoxia-Derived Exosomes Promote Lung Adenocarcinoma by Regulating HS3ST1-GPC4-Mediated Glycolysis
Objective: The diagnosis of lung adenocarcinoma (LUAD) is often delayed due to the typically asymptomatic nature of the early-stage disease, causing advanced-stage LUAD diagnosis in most patients. Hypoxia is widely recognized as a driving force in cancer progression. Exosomes originating from hypoxi...
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MDPI AG
2024-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/4/695 |
| _version_ | 1797298670418264064 |
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| author | Xianxiu Ji Ren Zhu Caixia Gao Huikang Xie Xiaomei Gong Jie Luo |
| author_facet | Xianxiu Ji Ren Zhu Caixia Gao Huikang Xie Xiaomei Gong Jie Luo |
| author_sort | Xianxiu Ji |
| collection | DOAJ |
| description | Objective: The diagnosis of lung adenocarcinoma (LUAD) is often delayed due to the typically asymptomatic nature of the early-stage disease, causing advanced-stage LUAD diagnosis in most patients. Hypoxia is widely recognized as a driving force in cancer progression. Exosomes originating from hypoxic tumor cells promote tumorigenesis by influencing glycolysis, migration, invasion, and immune infiltration. Given these insights, our study aimed to explore the role of hypoxia-derived exosomal long non-coding RNA (lncRNA) OIP5-AS1 in LUAD cell lines and mouse models. Materials and Methods: Exosomes were meticulously isolated and authenticated based on their morphology and biomarkers. The interaction between heparan sulfate (glucosamine) 3-O-sulfotransferase 1 (HS3ST1) and Glypican 4 (GPC4) was examined using immunoprecipitation. The influence of the hypoxia-derived exosomal lncRNA OIP5-AS1 on glycolysis was assessed in LUAD cell lines. The effect of the hypoxia-derived exosomal lncRNA OIP5-AS1 on cell proliferation and metastasis was evaluated using colony formation, cell viability, cell cycle, and apoptosis analyses. Its effects on tumor size were confirmed in xenograft animal models. Results: Our study revealed the mechanism of the hypoxia-derived exosomal lncRNA OIP5-AS1 in LUAD progression. We discovered that GPC4 promotes HS3ST1-mediated glycolysis and that the hypoxia-derived exosomal lncRNA OIP5-AS1 enhances glycolysis by regulating miR-200c-3p in LUAD cells. Notably, this lncRNA stimulates LUAD cell proliferation and metastasis and fosters LUAD tumor size via miR-200c-3p. Our findings underscore the potential role of the hypoxia-derived exosomal lncRNA OIP5-AS1 in LUAD progression. Conclusions: The hypoxia-derived exosomal lncRNA OIP5-AS1 promotes LUAD by regulating HS3ST1-GPC4-mediated glycolysis via miR-200c-3p. |
| first_indexed | 2024-03-07T22:38:23Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-07T22:38:23Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-17eef28cf98f40acaad05c67a94a8fcd2024-02-23T15:10:38ZengMDPI AGCancers2072-66942024-02-0116469510.3390/cancers16040695Hypoxia-Derived Exosomes Promote Lung Adenocarcinoma by Regulating HS3ST1-GPC4-Mediated GlycolysisXianxiu Ji0Ren Zhu1Caixia Gao2Huikang Xie3Xiaomei Gong4Jie Luo5Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, ChinaDepartment of Medical Administration, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, ChinaDepartment of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, ChinaDepartment of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, ChinaDepartment of Radiation Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, ChinaDepartment of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, ChinaObjective: The diagnosis of lung adenocarcinoma (LUAD) is often delayed due to the typically asymptomatic nature of the early-stage disease, causing advanced-stage LUAD diagnosis in most patients. Hypoxia is widely recognized as a driving force in cancer progression. Exosomes originating from hypoxic tumor cells promote tumorigenesis by influencing glycolysis, migration, invasion, and immune infiltration. Given these insights, our study aimed to explore the role of hypoxia-derived exosomal long non-coding RNA (lncRNA) OIP5-AS1 in LUAD cell lines and mouse models. Materials and Methods: Exosomes were meticulously isolated and authenticated based on their morphology and biomarkers. The interaction between heparan sulfate (glucosamine) 3-O-sulfotransferase 1 (HS3ST1) and Glypican 4 (GPC4) was examined using immunoprecipitation. The influence of the hypoxia-derived exosomal lncRNA OIP5-AS1 on glycolysis was assessed in LUAD cell lines. The effect of the hypoxia-derived exosomal lncRNA OIP5-AS1 on cell proliferation and metastasis was evaluated using colony formation, cell viability, cell cycle, and apoptosis analyses. Its effects on tumor size were confirmed in xenograft animal models. Results: Our study revealed the mechanism of the hypoxia-derived exosomal lncRNA OIP5-AS1 in LUAD progression. We discovered that GPC4 promotes HS3ST1-mediated glycolysis and that the hypoxia-derived exosomal lncRNA OIP5-AS1 enhances glycolysis by regulating miR-200c-3p in LUAD cells. Notably, this lncRNA stimulates LUAD cell proliferation and metastasis and fosters LUAD tumor size via miR-200c-3p. Our findings underscore the potential role of the hypoxia-derived exosomal lncRNA OIP5-AS1 in LUAD progression. Conclusions: The hypoxia-derived exosomal lncRNA OIP5-AS1 promotes LUAD by regulating HS3ST1-GPC4-mediated glycolysis via miR-200c-3p.https://www.mdpi.com/2072-6694/16/4/695lung adenocarcinoma (LUAD)lncRNAglycolysismiRNAHS3ST1GPC4 |
| spellingShingle | Xianxiu Ji Ren Zhu Caixia Gao Huikang Xie Xiaomei Gong Jie Luo Hypoxia-Derived Exosomes Promote Lung Adenocarcinoma by Regulating HS3ST1-GPC4-Mediated Glycolysis Cancers lung adenocarcinoma (LUAD) lncRNA glycolysis miRNA HS3ST1 GPC4 |
| title | Hypoxia-Derived Exosomes Promote Lung Adenocarcinoma by Regulating HS3ST1-GPC4-Mediated Glycolysis |
| title_full | Hypoxia-Derived Exosomes Promote Lung Adenocarcinoma by Regulating HS3ST1-GPC4-Mediated Glycolysis |
| title_fullStr | Hypoxia-Derived Exosomes Promote Lung Adenocarcinoma by Regulating HS3ST1-GPC4-Mediated Glycolysis |
| title_full_unstemmed | Hypoxia-Derived Exosomes Promote Lung Adenocarcinoma by Regulating HS3ST1-GPC4-Mediated Glycolysis |
| title_short | Hypoxia-Derived Exosomes Promote Lung Adenocarcinoma by Regulating HS3ST1-GPC4-Mediated Glycolysis |
| title_sort | hypoxia derived exosomes promote lung adenocarcinoma by regulating hs3st1 gpc4 mediated glycolysis |
| topic | lung adenocarcinoma (LUAD) lncRNA glycolysis miRNA HS3ST1 GPC4 |
| url | https://www.mdpi.com/2072-6694/16/4/695 |
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