Down-Regulation of miR-101 Contributes to Rheumatic Heart Disease Through Up-Regulating TLR2

Background: RHD is an autoimmune disease that arises following infection by S. pyogenes and imposes a heavy burden on public health. Material/Methods: We detected 11 selected miRNAs expressed in the cardiac tissues of 11 RHD patients and 11 controls. By employing dual-luciferase assay and Western blot, we identified the relationship between TLR2 and miR-101 and miR-101. We used ELISA to test the concentration of TNF-alpha, IL-1 beta, and IL-6. Results: In cardiac tissue of RHD patients, miR-101 was significantly down-regulated (p=0.011). Ectopically expressed miR-101 repressed the luciferase activity by 27% through targeting TLR2 3'UTR. Combined with the results of Western blot, we confirmed that TLR2 is a direct target gene of miR-101. miR-101 knock-down is related to over-stimulated immune response in PGN-activated THP-1 cells. We detected a significantly higher concentration of TNF-alpha (p=0.0017), IL-1 beta (p=0.015), and IL-6 (p=0.014) in serum samples. TLR2 had a higher expression in patients in the protein level rather than the mRNA level, indicating that post-transcriptional regulation factors play a crucial role in regulating TLR2 expression. Conclusions: The present study confirmed that miR-101 targets TLR2 3'UTR and represses TLR2 expression. This work also found an association between down-regulated miR-101 and rheumatic heart disease.