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miRNA Therapy in Laboratory Models of Acute Spinal Cord Injury in Rodents: A Meta-analysis

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Abstract

miRNA therapy is popularly investigated in treating acute spinal cord injury (SCI) and offers a significant prospect for the treatment of acute SCI. We aimed to provide pre-clinical validations of miRNA in the treatment of SCI. A systematic search of EMBASE, PubMed, Web of Science, the Cochrane Library, and Scopus databases was performed. Rats, which were the most used animals (70%, n = 46 articles), receiving miRNA therapy got prominent recovery in SCI models [BBB score, SMD 3.90, 95% CI 3.08–4.73, p < 0.01]. Locomotor function of fore and hind limbs in SCI mice receiving miRNA therapy (30%, n = 19 articles) [grip strength, SMD 3.22, 95% CI 2.14–4.26; p < 0.01; BBB score, SMD 3.47, 95% CI 2.38–4.56, p < 0.01; BMS, SMD 2.27, 95% CI 1.34–3.20, p < 0.01] also recovered better than mice in control group. Then, we conducted the subgroup analysis and did find that high-quality articles trended to report non-therapeutic effect of miRNA. Furtherly, we analyzed 46 miRNAs, including 9 miRNA families (miR-21-5p/34a-3p/124-3p/126-3p/223-3p/543-3p/30-3p/136-3p/15-5p), among which miR-30-3p/136-3p/15-5p family were not effective in recovering locomotor function of rats. Conclusively, miRNAs are curative drugs for SCI, however, appropriate miRNA carrier and which miRNA is the most efficacious for SCI should be furtherly investigated.

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YCS and YW: Conceptualization, YW and HXY: methodology, YW and HXY: investigation, YW: software, YW and HXY: formal analysis, YW and YCS: writing—original draft, YCS: writing—review & editing, YW and YCS: supervision. All authors read and approved the final manuscript.

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Correspondence to Yang Wang.

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Supplementary file1 (DOCX 16 KB) Additional file 1. Search strategy

Supplementary file2 (DOCX 21 KB) Additional file 2. miRNA sequence

Supplementary file3 (DOCX 29 KB) Additional file 3. PRISMA 2009 Checklist

Supplementary file4 (DOC 37 KB) Additional file 4. Article selection process

10571_2022_1235_MOESM5_ESM.pdf

Supplementary file5 (PDF 614 KB) Additional file 5. TSAs of the effect of exosomes on locomotor recovery after SCI. A The adjusted required information size is based on a median value of mean BBB scores of 3.90, an overall significance level (α) of 0.05, a type II risk (β) of 0.1 (power 90%), and equals 423 rats (vertical dotted red line). The cumulative Z-curve (solid blue line) connected by individual studies (small squares) crosses the upper O'Brien–Fleming monitoring boundary of benefit (descending dotted red line). B The adjusted required information size is based on the least value of mean BBB scores of 1, an overall significance level (α) of 0.05, a type II risk (β) of 0.1 (power 90%), and equals 2117 rats (vertical dotted red line). The cumulative Z-curve (solid blue line) connected by individual studies (small squares) crosses the upper O'Brien–Fleming monitoring boundary of benefit (descending dotted red line)

Supplementary file6 (PDF 1347 KB) Additional file 6. Funnel plot for the first assessment

Supplementary file7 (PDF 1358 KB) Additional file 7. Funnel plot for the last assessment

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Supplementary file8 (PDF 902 KB) Additional file 8. Funnel plot for the strength of pair limbs (A), left fore limbs (B) and right fore limbs (C)

Supplementary file9 (PDF 1193 KB) Additional file 9. Funnel plot for BBB score of mice at the 28th day post-injury

10571_2022_1235_MOESM10_ESM.pdf

Supplementary file10 (PDF 622 KB) Additional file 10. Funnel plot for BBB score of mice at the moment 35th day post-injury

Supplementary file11 (PDF 9347 KB) Additional file 11. The distribution of microRNAs in human chromosomes

Supplementary file12 (PDF 110 KB) Additional file 12. Number of target genes involved in signaling pathways

Supplementary file13 (PDF 618 KB) Additional file 13. Signaling pathways impacted by single microRNA

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Wang, Y., Yi, H. & Song, Y. miRNA Therapy in Laboratory Models of Acute Spinal Cord Injury in Rodents: A Meta-analysis. Cell Mol Neurobiol 43, 1147–1161 (2023). https://doi.org/10.1007/s10571-022-01235-2

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  • DOI: https://doi.org/10.1007/s10571-022-01235-2

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