Upregulation of Src by lncRNA Modulates FAK-dependent ErbB Signaling in Hepatocellular Carcinoma
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Abstract
Objective: To investigate Src expression in hepatocellular carcinoma (HCC) using bioinformatics approaches, focusing on its modulation of focal adhesion kinase (FAK/PTK2) via ErbB signaling and the regulatory role of long non-coding RNAs (lncRNAs). Methods: Fifty-five EGFR pathway genes extracted from QuickGO were uploaded to the BGI Multi-Omics Platform to generate FPKM matrices of tumor and adjacent tissue. Differentially expressed genes (DEGs) were defined by q < 0.05 and |log₂FC| > 1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed with DAVID; a protein–protein interaction (PPI) network was constructed in STRING and Cytoscape, and the top 12 hub genes were selected by degree. The same platform generated a hierarchical clustering heatmap and GO level-2 classification. Tumor Immune Estimation Resource 2.0 (TIMER2.0) was used to profile Src expression across cancers, HCC survival, and immune infiltration. Src/miRNA/lncRNA expression matrices were exported; transcripts with q < 0.05 were filtered in Excel, and a lncRNA-miRNA-Src competing endogenous RNA (ceRNA) network was built and visualized. Results: Src was overexpressed in HCC. It enhanced FAK activity and ErbB signaling, thereby accelerating HCC initiation and progression. Src activity correlates tightly with tumor aggressiveness. lncRNAs up-regulated Src and positively associate with angiogenesis, proliferation, and metastasis in HCC. Conclusion: High Src expression predicts poor prognosis in HCC. LncRNAs modulate Src levels and ErbB pathway activity.
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