HIF-1α-mediated LAMC1 overexpression is an unfavorable predictor of prognosis for glioma patients: evidence from pan-cancer analysis and validation experiments

Jianrong Bai ^1,2, Yangyang Zhao ^3,4, Kaijia Shi ³

¹Department of Pathology and Pathophysiology, School of Basic Medicine Sciences, Guangdong Medical University, Zhanjiang, 524023, China.
²Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, 215000, China.
³Department of Oncology of the First Affiliated Hospital & Cancer Institute, Hainan Medical University, Haikou, 570102, China.
⁴Emergency and Trauma College, Hainan Medical University, Haikou, 571199, China.
⁵Department of Oncology of the First Affiliated Hospital & Cancer Institute, Hainan Medical University, Haikou, 570102, China. hy0203141@hainmc.edu.cn.
⁶Department of Pathology and Pathophysiology, School of Basic Medicine Sciences, Guangdong Medical University, Zhanjiang, 524023, China. wei_jie@hainmc.edu.cn.
⁷Department of Oncology of the First Affiliated Hospital & Cancer Institute, Hainan Medical University, Haikou, 570102, China. wei_jie@hainmc.edu.cn.
⁸Emergency and Trauma College, Hainan Medical University, Haikou, 571199, China. wei_jie@hainmc.edu.cn.
⁹Department of Pathology and Pathophysiology, School of Basic Medicine Sciences, Guangdong Medical University, Zhanjiang, 524023, China. shenzh@gdmu.edu.cn.

⁰Department of Pathology and Pathophysiology, School of Basic Medicine Sciences, Guangdong Medical University, Zhanjiang, 524023, China.

Journal of Translational Medicine +

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April 27, 2024

View abstract on PubMed

Summary

High expression of Laminin subunit gamma-1 (LAMC1) in cancers, particularly gliomas, correlates with poor prognosis. Targeting the hypoxia-inducible factor-1α (HIF-1α)/LAMC1 pathway offers a potential new strategy for glioma treatment.

Area Of Science

Oncology
Molecular Biology
Bioinformatics

Background

Laminin subunit gamma-1 (LAMC1) is a key extracellular matrix molecule in the tumor microenvironment.
The biological functions and clinical significance of LAMC1 in various cancers are not fully understood.

Purpose Of The Study

To comprehensively analyze LAMC1 gene expression and its clinical relevance across pan-cancer datasets.
To investigate the association and regulatory mechanism between hypoxia-inducible factor-1α (HIF-1α) and LAMC1 in cancer, with a focus on glioma.

Main Methods

Bioinformatics analysis of LAMC1 in The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas datasets.
Validation of LAMC1 expression in glioma tissues and cell lines.
Exploration of the HIF-1α/LAMC1 regulatory axis under hypoxic conditions.

Main Results

Elevated LAMC1 expression was observed in most TCGA cancers, including glioma, correlating with poor prognosis and clinicopathological features.
LAMC1 knockdown inhibited glioma cell proliferation and invasion, while overexpression promoted these processes.
HIF-1α directly upregulated LAMC1 promoter activity, and hypoxia enhanced both HIF-1α and LAMC1 expression, which was reversed by a HIF-1α inhibitor.

Conclusions

High LAMC1 expression in solid tumors like gliomas indicates a poor prognosis.
The HIF-1α/LAMC1 signaling pathway, activated by the hypoxic tumor microenvironment, promotes glioma progression.
Targeting the HIF-1α/LAMC1 pathway presents a promising therapeutic strategy for glioma.

Keywords:

Gliomas HIF-1α LAMC1 Pan-cancer Prognosis

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