HIF-1α-mediated LAMC1 Expression is an Unfavorable Predictor of Prognosis for Glioma Patients: Evidence from Pan-Cancer Analysis and Validation Experiments

Background Laminin subunit gamma-1 (LAMC1) is a major extracellular matrix molecule involved in the tumor microenvironment. Knowledge of the biological features and clinical relevance of LAMC1 in cancers remains limited. Methods We conducted comprehensive bioinformatics analysis of LAMC1 gene expression and clinical relevance in pan-cancer datasets of public databases and validated LAMC1 expression in glioma tissues and cell lines. The association and regulatory mechanism between hypoxia inducible factor-1α ( HIF-1α ) and LAMC1 expression were explored. Results LAMC1 expression in most cancers in The Cancer Genome Atlas (TCGA) including glioma was significantly higher than that in normal tissues, which had a poor prognosis and were related to various clinicopathological features. Data from the Chinese Glioma Genome Atlas also showed high expression of LAMC1 in glioma associated with poor prognoses. In clinical glioma tissues, LAMC1 protein was highly expressed and correlated to poor overall survival. LAMC1 knockdown in Hs683 glioma cells attenuated cell proliferation, migration, and invasion. Most TCGA cancers including glioma showed enhancement of HIF-1α expression. HIF-1α expression was positively related to LAMC1 expression in glioma. HIF-1α directly upregulated LAMC1 promotor activity. Hypoxia (2% O 2 )-treated Hs683 and U251 cells exhibited upregulated HIF-1α and LAMC1 expression, which was significantly attenuated by HIF-1α inhibitor YC-1 and accompanied by attenuated cell proliferation and invasion. Conclusions High expression of LAMC1 in most cancers including glioma suggests a poor prognosis. Moreover, activation of the HIF-1α/LAMC1 axis in a hypoxic microenvironment promotes glioma progression and may be a therapeutic target in cancer.