The expression of SERPINE1 in colon cancer and its regulatory network and prognostic value

Hepatocellular carcinoma (HCC) is one of the most deadly malignancies. Due to the late detection of HCC, the treatment are not satisfactory, accompanied by poor prognosis. Therefore, early detection has important value for HCC treatment. MicroRNAs (miRNAs), the intercellular communication in the tumor microenvironment, are widely accepted as molecular markers of HCC. However, there are few studies on miRNAs involved in the crosstalk between cancer-associated fibroblast (CAF) and HCC cells. In the study, transcriptome sequencing, siRNA, co-culture, reverse transcription quantitative real-time PCR (RT-qPCR), western blot, dual-luciferase reporter system, and xenograft tumor model, were used to explore the role of miR-642a-3p/SERPINE1 axis in HCC progression. The results showed that in co-culture with CAF, the expression of SERPINE1 mRNA decreased, whereas miR-642a-3p expression increased in Huh7 cells. SERPINE1 knockdown significantly enhanced the invasion ability and increased miR-642a-3p expression in Huh7 cells. Dual-luciferase reporter assay discovered that miR-642a-3p had a binding effect with SERPINE1, suggesting that SERPINE1 was a target of miR-642a-3p. In addition, miR-642a-3p mimics inhibited SERPINE1 expression and promoted the migration, invasion, and EMT of Huh7 cells, whereas miR-642a-3p inhibitor had the opposite effect. More importantly, miR-642a-3p knockdown inhibited the proliferation and spread of xenograft tumors in the liver. miR-642a-3p knockdown significantly inhibited epithelial-mesenchymal transition (EMT) in the liver. These findings reveal that the miR-642a-3p/SERPINE1 axis plays an important role in the invasion and metastasis of HCC, and can be used as a novel therapeutic target for HCC.

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Identification and functional analysis of lactic acid metabolism-related differentially expressed genes in hepatocellular carcinoma

Li,

Qian,

Bao

2024

Front. Genet.

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Background: Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality rate that seriously threatens human health. We aimed to investigate the expression, prognostic value, and immune cell infiltration of lactic acid metabolism-related genes (LAMRGs) in HCC using bioinformatics.Methods: The HCC database (The Cancer Genome Atlas–Liver Hepatocellular Carcinoma) was downloaded from the Cancer Genome Atlas (TCGA). Differentially expressed genes (DEGs) between normal and tumor groups were identified. The LAMRGs were obtained from literature and GeneCards and MSigDB databases. Lactic acid metabolism-related differentially expressed genes (LAMRDEGs) in HCC were screened from the DEGs and LAMRGs. Functional enrichment analyses of the screened LAMRDEGs were further conducted using Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA). The genes were used in multivariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses to construct a prognostic model. Then, a protein-protein interaction network was constructed using STRING and CTD databases. Furthermore, the CIBERSORTx online database was used to assess the relationship between immune cell infiltration and hub genes.Results: Twenty-eight lactic acid metabolism-related differentially expressed genes (LAMRDEGs) were identified. The GO and KEGG analyses showed that the LAMRDEGs were related to the prognosis of HCC. The GSEA indicated that the LAMRDEGs were significantly enriched in tumor related pathways. In the multivariate Cox regression analysis, 14 key genes (E2F1, SERPINE1, GYS2, SPP1, PCK1, CCNB1, CYP2C9, IGFBP3, KDM8, RCAN1, ALPL, FBP1, NQO1, and LCAT) were found to be independent prognostic factors of HCC. Finally, the LASSO and Cox regression analyses showed that six key genes (SERPINE1, SPP1, CCNB1, CYP2C9, NQO1, and LCAT) were associated with HCC prognosis. Moreover, the correlation analyses revealed that the expression of the six key genes were associated with immune infiltrates of HCC.Conclusion: The LAMRDEGs can predict the prognosis and may be associated with immune cells infiltration in patients with HCC. These genes might be the promising biomarkers for the prognosis and treatment of HCC.

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The expression of SERPINE1 in colon cancer and its regulatory network and prognostic value

Cited by 3 publications

References 42 publications

Helicobacter pylori impacts the expression of immune checkpoint molecules in gastric cancer via up-regulating SERPINE1

Helicobacter pylori impacts the expression of immune checkpoint molecules in gastric cancer via up-regulating SERPINE1

CAF-related miR-642a-3p supports the migration, invasion, and EMT of hepatocellular carcinoma by targeting SERPINE1

Identification and functional analysis of lactic acid metabolism-related differentially expressed genes in hepatocellular carcinoma

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