Urokinase-type plasminogen activator and related microRNAs in hepatocellular carcinoma; a bioinformatic based study
Year: 2025
Type: article
Abstract: Urokinase-type plasminogen activator and related microRNAs in hepatocellular carcinoma; a bioinformatic based study H epatocellular carcinoma (HCC), which constitutes approx- imately 90% of primary liver cancers, is one of the most prevalent cancers globally, ranking sixth in incidence and third in cancer-related mortality [1,2].HCC remains a significant global health concern, with rising incidence rates observed in both developed and developing countries [3,4].The pathogenesis of HCC involves a complex array of molecular alterations, such as cell cycle dysregulation, immune modulation, DNA methylation changes, epithelial-mesenchymal transition (EMT), and microRNA (miRNA) dysregulation [5].HCC is characterized by poor overall survival and a high recurrence rate [4].Despite notable advances in surgical interventions, Objectives: Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide.Urokinase-type plasminogen activator (uPA), which is encoded by the PLAU gene, is a serine protease involved in the degradation of the extracellular matrix.Increasing evidence indicates that PLAU is overexpressed in various cancers and is associated with poor prognosis, making it a potential biomarker for cancer.However, its potential role in HCC remains unclear.Therefore, this study aimed to investigate the role of PLAU and related microRNAs in HCC using multiple bioinformatics tools.Methods: PLAU expression was evaluated using the TNMplot and GEPIA2 databases.Promoter methylation levels were assessed through UALCAN.Survival analysis (overall survival (OS) and recurrence-free survival (RFS) rates), was conducted using the Kaplan-Meier Plotter.Protein-protein interaction networks were examined with STRING.Target miRNAs were identified using TargetScan 8.0.Differential expression, survival analysis, and co-expression of miRNAs were investigated using ENCORI.Results: PLAU expression was significantly upregulated in liver hepatocellular carcinoma (LIHC) compared to normal tissues (p<0.05).Promoter methylation level of PLAU was significantly increased (hypermethylation) in LIHC tissues (p=5.43×10-¹²).Elevated PLAU expression was not associated with OS (p=0.16) and RFS (p=0.28)rates.hsa-miR-181a-5p, hsa-miR-181b-5p, hsa-miR-181c-5p, and hsa-miR-181d-5p were positively correlated with PLAU in LIHC tissue (p<0.05).The hsa-miR-181a-5p and hsa-miR-181b-5p were up-regulated in LIHC (p<0.05). Conclusion:In conclusion, our study highlights the potential role of PLAU and its related miRNAs (hsa-miR-181a-5p and hsa-miR-181b-5p) in HCC.However, elevated PLAU expression did not correlate with survival rates, indicating its involvement in tumor development but no prognostic significance.Further applicable studies are needed on this subject.
Author: Gonul Seyda Seydel
Institution: Niğde Ömer Halisdemir Üniversitesi
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4415438638