Bone marrow mesenchymal stem cells (BMSCs) have strong regenerative potential and show good application prospects for treating clinical diseases. However, in the process of BMSC
transplantation for treating ischemic and hypoxic diseases, BMSCs have high rates of apoptosis in the hypoxic microenvironment of
transplantation, which significantly affects the
transplantation efficacy. Our previous studies have confirmed the key role of
long non-coding RNA Tmem235 (
LncRNA Tmem235) in the process of
hypoxia-induced BMSC apoptosis and its downstream regulatory mechanism, but the upstream mechanism by which
hypoxia regulates
LncRNA Tmem235 expression to induce BMSC apoptosis is still unclear. Under hypoxic conditions, we found that the level of
LncRNA Tmem235 promoter
histone H3 lysine 27 trimethylation modification (H3K27me3) was significantly increased by CHIP-qPCR. Moreover, H3K27me3 cooperated with
LncRNA Tmem235 promoter DNA methylation to inhibit the expression of
LncRNA Tmem235 and promote apoptosis of BMSCs. To study the mechanism of
hypoxia-induced modification of
LncRNA Tmem235 promoter H3K27me3 in the
hypoxia model of BMSCs, we detected the expression of H3K27 methylase and
histone demethylase and found that only
histone methylase enhancer of zeste homolog 2 (EZH2) expression was significantly upregulated. Knockdown of EZH2 significantly decreased the level of H3K27me3 modification in the
LncRNA Tmem235 promoter. The EZH2 promoter region contains a
hypoxia-responsive
element (HRE) that interacts with
hypoxia-inducible factor-1alpha (HIF-1α), which is overexpressed under hypoxic conditions, thereby promoting its overexpression. In summary,
hypoxia promotes the modification of the
LncRNA Tmem235 promoter H3K27me3 through the HIF-1α/EZH2 signaling axis, inhibits the expression of
LncRNA Tmem235, and leads to hypoxic apoptosis of BMSCs. Our findings improve the regulatory mechanism of
LncRNA Tmem235 during hypoxic apoptosis of BMSCs and provide a more complete theoretical pathway for targeting
LncRNA to inhibit hypoxic apoptosis of BMSCs.