Hypoxia-Derived Exosomes Promote Lung Adenocarcinoma by Regulating HS3ST1-GPC4-Mediated Glycolysis

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2024 Feb 24

PMID 38398086

Authors

Xianxiu Ji

Ren Zhu

Caixia Gao

Huikang Xie

Xiaomei Gong

Jie Luo

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Hypoxia studies in non‑small cell lung cancer: Pathogenesis and clinical implications (Review).

Zhou S, Sun J, Zhu W, Yang Z, Wang P, Zeng Y Oncol Rep. 2025; 53(2.

PMID: 39749693 PMC: 11715622. DOI: 10.3892/or.2024.8862.

Exosomal microRNAs in lung cancer: a narrative review.

Zhang Z, Lin F, Wu W, Jiang J, Zhang C, Qin D Transl Cancer Res. 2024; 13(6):3090-3105.

PMID: 38988916 PMC: 11231775. DOI: 10.21037/tcr-23-2319.

Advancements and trends in exosome research in lung cancer from a bibliometric analysis (2004-2023).

Zhong W, Zhao X, Zhang X, Xu Y, Liu M, Yang X Front Oncol. 2024; 14:1358101.

PMID: 38690166 PMC: 11058220. DOI: 10.3389/fonc.2024.1358101.

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