Plasma Levels of MicroRNA Let-7c-5p May Predict Risk of Acute Chest Syndrome in Patients with Sickle Cell Disease
Abstract
1. Introduction
2. Results
2.1. Characteristics of Subjects Used for RNA Sequencing
2.2. MicroRNA Contents of Small EVs in Subjects with SCD
2.3. Characteristics of Subjects Used for RT-qPCR of Let-7c-5p (Replication Cohort)
2.4. Let-7c-5p Levels in Subjects with SCD
3. Discussion
4. Materials and Methods
4.1. Subjects
4.2. Isolation of Platelet-Free Plasma
4.3. Small RNA Isolation and Its Sequencing in Discovery Cohort
4.4. Sequencing Data Analysis
4.5. MicroRNA Extraction and RT-qPCR in Replication Cohort
4.6. Statistical Analyses
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
SCD | Sickle cell disease |
ACS | Acute chest syndrome |
RT-qPCR | Quantitative reverse transcription polymerase chain reaction |
EV | Extracellular vesicle |
NS | Not Significant |
sPLA2 | Secretory phospholipase A2 |
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No History of ACS (n = 12) | History of ACS (n = 17) | p-Value | |
---|---|---|---|
Demographics | |||
Age (years), median (range) | 14 (3–18) | 14 (5–20) | NS |
Sex, n (%) | NS | ||
Male | 7 (58) | 11 (65) | |
Female | 5 (42) | 6 (35) | |
Hematologic Values | Median (25%, 75%) | Median (25%, 75%) | |
White blood cell count (×103/µL) | 9.2 (8.4, 14.3) | 11.8 (10.7, 14.6) | NS |
Hemoglobin (g/dL) | 8.4 (8.1, 9.1) | 9.3 (7.8, 10.7) | NS |
MCV (fL) | 84.2 (77.3, 93.8) | 95.2 (88.3, 101) | <0.05 |
Reticulocyte (×103/µL) | 266 (212, 384) | 249(161, 303) | NS |
Platelet (×103/µL) | 404 (291, 462) | 414 (400, 458) | NS |
Bilirubin (mg/dL) | 3.0 (2.0, 4.6) | 2.9 (1.8, 6.3) | NS |
Hemoglobin Genotype, n (%) | |||
SS | 11 (92) | 15 (88) | |
Sβ0Thal | 0 | 1 (6) | |
SC | 1 (8) | 1 (6) | |
Clinical Characteristics | |||
Rate of ACS (n/year) | 0 | 0.17 (0.08, 0.23) | <0.05 |
Absolute ACS, n | 0 | 1 (1, 3.5) | <0.005 |
Rate of pain (n/year) | 0 (0, 0.23) | 0.18 (0.08, 0.65) | NS |
Absolute pain, n | 0 (0, 3.5) | 2 (1, 9) | NS |
Hydroxyurea, n (%) | 3 (25) | 12 (71) | <0.05 |
Asthma, n (%) | 0 | 5 (29) | <0.05 |
Obstructive sleep apnea (%) | 6 (50) | 4 (24) | NS |
Splenectomy, n (%) | 3 (25) | 4 (24) | NS |
Cholecystectomy, n (%) | 1 (8) | 4 (24) | NS |
No History of ACS (n = 6) | History of ACS (n = 10) | p-Value | |
---|---|---|---|
Demographics | |||
Age (years), median (range) | 4 (4–8) | 8 (4–9) | NS |
Sex, n (%) | NS | ||
Male | 3 (50) | 3 (30) | |
Female | 3 (50) | 7 (70) | |
Hematologic Values | Median (25%, 75%) | Median (25%, 75%) | |
White blood cell count (×103/µL) | 12.3 (10.6, 13.2) | 10.9 (9.9, 12.4) | NS |
Hemoglobin (g/dL) | 8.3 (8.2, 8.7) | 9.2 (8.0, 9.7) | NS |
MCV (fL) | 88.6 (84.1, 92.4) | 93.5 (91.4, 98.0) | NS |
Reticulocyte (×103/µL) | 258 (217, 298) | 231 (203, 259) | NS |
Platelet (×103/µL) | 402 (282, 509) | 429 (383, 459) | NS |
Bilirubin (mg/dL) | 1.9 (1.9, 2.6) | 3.1 (2.1, 4.7) | NS |
Hemoglobin Genotype, n (%) | |||
SS | 5 (83) | 10 (100) | |
Sβ0Thal | 1 (14) | 0 (0) | |
Clinical Characteristics | |||
Rate of ACS (n/year) | 0 | 0.25 (0.20, 0.25) | <0.005 |
Absolute ACS, n | 0 | 1.00 (1.00, 2.75) | <0.005 |
Rate of pain (n/year) | 0.6 (0, 0.2) | 0.5 (0.1, 0.8) | NS |
Absolute pain, n | 0.5 (0, 1.0) | 2.0 (1.0, 7.0) | NS |
Hydroxyurea, n (%) | 1 (12) | 6 (60) | <0.05 |
Asthma, n (%) | 1 (12) | 3 (30) | NS |
Obstructive sleep apnea (%) | 0 | 4 (40) | <0.05 |
Splenectomy, n (%) | 1 (12) | 2 (20) | NS |
Cholecystectomy, n (%) | 0 | 1 (10) | NS |
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Fan, J.; Gemel, J.; Beyer, E.C.; Lapping-Carr, G. Plasma Levels of MicroRNA Let-7c-5p May Predict Risk of Acute Chest Syndrome in Patients with Sickle Cell Disease. Int. J. Mol. Sci. 2025, 26, 3831. https://doi.org/10.3390/ijms26083831
Fan J, Gemel J, Beyer EC, Lapping-Carr G. Plasma Levels of MicroRNA Let-7c-5p May Predict Risk of Acute Chest Syndrome in Patients with Sickle Cell Disease. International Journal of Molecular Sciences. 2025; 26(8):3831. https://doi.org/10.3390/ijms26083831
Chicago/Turabian StyleFan, James, Joanna Gemel, Eric C. Beyer, and Gabrielle Lapping-Carr. 2025. "Plasma Levels of MicroRNA Let-7c-5p May Predict Risk of Acute Chest Syndrome in Patients with Sickle Cell Disease" International Journal of Molecular Sciences 26, no. 8: 3831. https://doi.org/10.3390/ijms26083831
APA StyleFan, J., Gemel, J., Beyer, E. C., & Lapping-Carr, G. (2025). Plasma Levels of MicroRNA Let-7c-5p May Predict Risk of Acute Chest Syndrome in Patients with Sickle Cell Disease. International Journal of Molecular Sciences, 26(8), 3831. https://doi.org/10.3390/ijms26083831