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Basic Research
Role and mechanism of CXCL5/CXCR2/VEGF pathway in angiogenesis of HBVrelated hepatocellular carcinoma
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Abstract:
Objective: To explore the role and mechanism of CXC chemokine ligand 5/CXC receptor 2/ vascular endothelial growth factor (CXCL5/CXCR2/VEGF) pathway in the angiogenesis of hepatitis B virus (HBV) -related hepatocellular carcinoma (HCC). Methods: Peripheral blood samples were collected from 10 HBV-DNA positive patients admitted to Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine between October 2022 and December 2022, including 5 cases of HCC and 5 cases of liver cirrhosis (LC). High-throughput RNA sequencing was used to detect and screen differentially expressed mRNAs. GO enrichment and KEGG pathway analysis were conducted to explore the biological functions and related signaling pathways of these differentially expressed genes. HCC HepG2 cells were conventionally cultured, and CXCL5 overexpression plasmid and control plasmid were transfected into HepG2 cells using transfection reagents. The cells were divided into a control group, an empty load group, and two CXCL5 overexpression groups (250 ng/mL and 520 ng/mL). The effects of CXCL5 overexpression on HepG2 cell proliferation (CCK-8 method), VEGF secretion (ELISA), tube formation ability (angiogenesis assay), mRNA and protein expression of CXCL5, CXCR2, VEGF (qPCR, Western blot), as well as VEGF expression immunofluorescence intensity were analyzed. Results: RNA sequencing results showed significant differences in mRNA expression in peripheral blood between HCC and LC patients. GO enrichment analysis revealed that these differentially expressed genes were mainly involved in cell development regulation, G proteincoupled receptor activity, extracellular region components, and receptor-ligand binding. KEGG pathway analysis revealed that these differentially expressed genes might participate in pathways related to the cytokine-receptor interactions, cAMP signaling and other cancer related pathways, neuroactive ligand-receptor interactions, and calcium signaling pathways. Overexpression of CXCL5 significantly promoted HepG2 cell proliferation (P < 0.05), VEGF secretion (P < 0.05), tube formation in human umbilical vein endothelial cells (HUVECs) (P < 0.05), and mRNA and protein expression of CXCL5, CXCR2, and VEGF (P < 0.05 or P < 0.01), as well as enhanced the immunofluorescence intensity of VEGF in HepG2 cells. Conclusion: CXCL5 may promote the proliferation of HepG2 cells and HUVEC angiogenesis through the CXCL5/CXCR2/VEGF axis.
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