Abstract
N6-methyl-adenosine (m6a) is involved in the occurrence and development of various diseases such as autogenic immune disease and tumors. Methyltransferases regulate primary (pri)-microRNA (miRNA/miR) processing by mediating m6a modifications, consequently affecting pathological processes including immune-related diseases by regulating both innate and adaptive immune cells. However, the roles of m6a on the biological functions of bone marrow mesenchymal stem cells (BMSCs) remain to be elucidated. The relative expression levels of methyltransferase-like 14 (METTL14) and other methyltransferases, demethylases, and miR-873 in bone samples from patients with osteoporosis and from normal individuals were measured by reverse transcription-quantitative PCR. Cell Counting Kit-8 assay was used to examine the proliferation of BMSCs. Co-immunoprecipitation (Co-IP) was used to investigate the binding of METTL14 to DiGeorge syndrome critical region 8 (DGCR8). RNA immunoprecipitation (RIP) was used to examine the binding of METTL14 to pri-miR-873. METTL14 and m6a modifications were highly detected in patients with osteoporosis compared with the controls. Co-IP results indicated that silencing of METTL14 reduced METTL14 and m6a modification levels in BMSCs. Downregulation of METTL14 significantly promoted the proliferation of BMSCs. RIP results suggested that METTL14/m6a methylation modification promoted the processing of pri-miR-873 by binding to DGCR8 in BMSCs. Furthermore, overexpression of miR-873 inhibited the proliferation of BMSCs. The results also showed that miR-873 mimics significantly inhibited the proliferation in small interfering (si)-METTL14 transfected BMSCs; however, miR-873 inhibitors markedly promoted the proliferation of si-METTL14 transfected BMSCs. METTL14 and m6a modifications were upregulated in osteoporosis samples. METTL14 promoted the processing of pri-miR-873 into mature miR-873 by regulating m6a modification. Furthermore, overexpression of miR-873 significantly inhibited the proliferation of BMSCs. Therefore, the METTL14/m6a/miR-873 axis may be a potential target for the treatment of osteoporosis.
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