HCV-Associated Exosomes Upregulate RUNXOR and RUNX1 Expressions to Promote MDSC Expansion and Suppressive Functions through STAT3–miR124 Axis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Subjects
2.2. Cell Isolation, Culture, and Flow Cytometric Analysis
2.3. Exosome Isolation and Purification
2.4. lncRNA and miRNA Arrays and RT-qPCR Validation
2.5. Transfection and Co-Culture Experiments
2.6. Statistical Analysis
3. Results
3.1. MDSCs Accumulate in Peripheral Blood during Chronic HCV Infection
3.2. RUNXOR and RUNX1 Are Upregulated in MDSCs during Chronic HCV Infection
3.3. Immunosuppressive Molecules Are Elevated in MDSCs during Chronic HCV Infection
3.4. MiR-124 Expression Negatively Correlates with STAT3 Levels in MDSCs during HCV Infection
3.5. RUNXOR and RUNX1 Regulate Each Other’s and Control miR-124 Expression via the STAT3 Signaling in MDSCs during HCV Infection
3.6. HCV-Associated Exosomes Regulate RUNXOR, RUNX1, and Suppressive Molecule Expressions in MDSCs
3.7. Cytarabine Regulates RUNXOR and Immunosuppressive Molecules in Healthy CD33+ Cells
3.8. Silencing RUNXOR and RUNX1 Expressions Reduce MDSC Frequencies and Suppressive Functions
4. Discussion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Subjects | Numbers | Age (Mean) | Gender (M/F) | Viral Load and Other Characteristics |
---|---|---|---|---|
HCV | 50 | 29–65 (46) | 39/11 | 17,000–17,000,000 IU/mL, 36GT1, 8GT2, 6GT3 |
HS | 54 | 22–64 (33) | 41/13 | All the tested negative for HCV, HBV and HIV |
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Thakuri, B.K.C.; Zhang, J.; Zhao, J.; Nguyen, L.N.; Nguyen, L.N.T.; Schank, M.; Khanal, S.; Dang, X.; Cao, D.; Lu, Z.; et al. HCV-Associated Exosomes Upregulate RUNXOR and RUNX1 Expressions to Promote MDSC Expansion and Suppressive Functions through STAT3–miR124 Axis. Cells 2020, 9, 2715. https://doi.org/10.3390/cells9122715
Thakuri BKC, Zhang J, Zhao J, Nguyen LN, Nguyen LNT, Schank M, Khanal S, Dang X, Cao D, Lu Z, et al. HCV-Associated Exosomes Upregulate RUNXOR and RUNX1 Expressions to Promote MDSC Expansion and Suppressive Functions through STAT3–miR124 Axis. Cells. 2020; 9(12):2715. https://doi.org/10.3390/cells9122715
Chicago/Turabian StyleThakuri, Bal Krishna Chand, Jinyu Zhang, Juan Zhao, Lam N. Nguyen, Lam N. T. Nguyen, Madison Schank, Sushant Khanal, Xindi Dang, Dechao Cao, Zeyuan Lu, and et al. 2020. "HCV-Associated Exosomes Upregulate RUNXOR and RUNX1 Expressions to Promote MDSC Expansion and Suppressive Functions through STAT3–miR124 Axis" Cells 9, no. 12: 2715. https://doi.org/10.3390/cells9122715