Hsa_circ_0000437 promotes the progression of rheumatic valvular heart disease by activating the mitogen-activated protein kinase signaling pathways after sponging let-7f-5p and targeting RAS-like proto-oncogene B.

Circular RNAs (circRNAs) are involved in cardiovascular disease development and progression. We identified has_circ_0000437 from three pairs of clinical samples using a circRNA microarray and predicted the has_circ_0000437 sponge let-7f-5p using bioinformatics. We expanded the sample to confirm the expression, correlation, and diagnostic value of has_circ_0000437, let-7f-5p and RAS-like proto-oncogene B (RALB) in rheumatic valvular heart disease (RVHD). The effects of has_circ_0000437 and let-7f-5p on biological function were observed in hVICs cells. To explore the molecular pathogenesis of has_circ_0000437 in the RVHD process, the target binding protein RAS-like proto-oncogene B (RALB) of has_circ_0000437 was obtained using label-free mass spectrometry and parallel reaction monitoring. The influence of the has_circ_0000437/let-7f-5p/RALB axis on the expression of mitogen-activated protein kinase (MAPK)-related proteins in the inflammatory signaling pathway predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) during RVHD was measured using Western blotting. We found that let-7f-5p was at low expression and negatively correlated with has_circ_0000437, which had a diagnostic value with an area under the curve of 0.998 after the combined diagnosis. Has_circ_0000437 and let-7f-5p had binding sites, and let-7f-5p alleviated the effect of has_circ_0000437 on the proliferation, migration, and cycle progression of hVICs. The inhibitory effect of has_circ_0000437 on hVICs apoptosis was diminished. Mechanism studies showed that has_circ_0000437 promotes the MAPK pathway through has_circ_0000437/let-7f-5p/RALB axis. These findings suggest that the has_circ_0000437/let-7f-5p/RALB axis promotes the MAPK pathway, proliferation, migration, and cycle progression in RVHD, inhibiting the apoptosis process, thereby promoting RVHD development. This pathway may suggest a target for RVHD diagnosis and treatment.