Background: Studies revealed that exosomes from IFN-α-treated liver non-parenchymal cells (IFN-exo) mediate antiviral activity. MiR-106b-3p has been shown to play a paradoxical role in disease progressing from different studies. However, its specific role in HBV-related hepatocellular carcinoma (HBV-HCC) and the underlying mechanism remains unclear.
Method: Huh7 cells transient transfected with plasmids of HBV-C2 and B3 were co-cultured with IFN-exo. Cell supernatants were collected to detect miR-106b-3p, HBsAg, HBeAg and HBV DNA levels. Cell proliferation, apoptosis, migration and invasion were analyzed. The putative targets of miR-106b-3p were identified by a dual-luciferase reporter system. The expression of PCGF3, migratory proteins(MMP2/9), and the PI3K/AKT signaling pathway-related proteins were assessed by western blot. The expression of PCGF3 mRNA was quantitative analyzed by using 52 pairs of paraffin-embedded tissues from HCC patients. siRNAs-PCGF3 were used to knocked-down PCGF3 expression.
Results: The expression of miR-106b-3p was significantly higher in THP-1 cells and supernatants treated with IFN-exo than those untreated. Significantly increased expression of miR-106b-3p and decreased expression of HBsAg and HBV DNA were observed in Huh7-C2/B3 cells treated with IFN-exo. In addition, miR-106b-3p was directly target to PCGF3. Scratch healing assay and transwell assay showed that either IFN-exo or miRNA-106-3p over-expression, or siRNAs-PCGF3 inhibited migration and invasion of Huh7-C2/B3 cells, and subsequently resulted in suppression of p-AKT/AKT and p-PI3K/PI3K. Notably, the expression level of PCGF3 was significantly lower in HBeAg (+)-HCC tumor tissues than HBeAg (-)-HCC tumor.
Conclusion: IFN-α-induced macrophage-derived miR-106b-3p inhibits HBV replication, HBV- Huh7 cells migration and invasion via regulating PCGF3/PI3K/AKT signaling axis. miR-106b-3p and PCGF3 were potential biomarkers in the prevention and treatment of HBV-HCC.
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http://dx.doi.org/10.3389/fcimb.2024.1421195 | DOI Listing |
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January 2025
Department of Bioengineering, Indian Institute of Science, Bengaluru, 560012, India.
Cancer metastasis involves cell migration from their primary organ foci into vascular channels, followed by dissemination to prospective colonization sites. Vascular entry of tumor cells or intravasation involves their breaching stromal and endothelial extracellular matrix (ECM) and the endothelial barriers. How the kinetics of this breach are confounded by chronic inflammatory stresses seen in diabetes and aging remains ill-investigated.
View Article and Find Full Text PDFMol Omics
January 2025
Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore 575018, India.
Lung cancer remains the leading cause of cancer-related deaths worldwide due to its poor prognosis. Despite significant advancements in the understanding of cancer development, improvements in diagnostic methods, and multimodal therapeutic regimens, the prognosis of lung cancer has still not improved. Therefore, it is reasonable to look for newer and alternative medicines for treatment.
View Article and Find Full Text PDFJ Cell Sci
January 2025
Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA.
Ligand binding to EGFR activates Rho family GTPases, triggering actin cytoskeleton reorganization, cell migration and invasion. Activated EGFR is also rapidly endocytosed but the role of EGFR endocytosis in cell motility is poorly understood. Hence, we used live-cell microscopy imaging to demonstrate that endogenous fluorescently labeled VAV2, a guanine nucleotide exchange factor for Rho GTPases, is co-endocytosed with EGFR in genome-edited human oral squamous cell carcinoma (HSC3) cells, an in vitro model for head-and-neck cancer where VAV2 is known to promote metastasis and associates with poor prognosis.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Oral Anatomy and Physiology, Jilin Provincial Key Laboratory of Oral Biomedical Engineering, Hospital of Stomatology, Jilin University, Changchun, China.
Oral squamous cell carcinoma (OSCC) is a highly aggressive and malignant tumor of oral cavity with a poor prognosis and high mortality due to the limitations of existing therapies. The significant role of tumor microenvironment (TME) in the initiation, development, and progression of OSCC has been widely recognized. Various cells in TME, including tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), T lymphocytes, tumor-associated neutrophils (TANs), myeloid-derived suppressor cells (MDSCs) and dendritic cells (DCs), form a complicated and important cellular network to modulate OSCC proliferation, invasion, migration, and angiogenesis by secreting RNAs, proteins, cytokines, and metabolites.
View Article and Find Full Text PDFJ Cancer
January 2025
Cancer Prevention and Treatment Institute of Chengdu, Department of Neurosurgery, Chengdu Fifth People's Hospital (The Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu 611137, China.
Glioblastoma (GBM), notorious for its poor prognosis, stands as a formidable challenge within the central nervous system tumor category, primarily due to its intricate pathology that encompasses stemness and the epithelial-mesenchymal transition (EMT). The ubiquity of S phase kinase-associated protein 2 (Skp2) overexpression in GBM, a protein implicated in both EMT and stemness traits, correlates with increased drug resistance, elevated tumor grades, and adverse outcomes. This investigation delves into the impact of Raddeanin A (RA), a triterpenoid compound extracted from Anemone raddeana Regel, on GBM, with a special focus on its influence over Skp2 expression levels.
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