Inhibition of microRNA‑16 protects mesenchymal stem cells against apoptosis.

Bone marrow‑derived mesenchymal stem cells (BM‑MSCs) have been used in experimental research and clinical trials for heart function restoration and cardiomyocyte regeneration. However, due to a hostile microenvironment created by ischemia, hypoxia and pro‑inflammatory factors, the survival rate of implanted BM‑MSCs remains low. Therefore, strategies that can promote BM‑MSC survival and prevent apoptosis are required. Previous studies have reported that microRNA‑16 (miR‑16) can inhibit cell proliferation by targeting several proteins and signal pathway, not only by inducing apoptosis. In the present study, it was investigated whether inhibition of miR‑16 reduced BM‑MSC apoptosis in a model of ischemia. Flow cytometry analysis revealed that BM‑MSCs underwent apoptosis in response to hypoxia/serum deprivation (SD). Additionally, in hypoxic/SD conditions, miR‑16 expression increased and B‑cell lymphoma (Bcl)‑2 protein expression decreased in BM‑MSCs. miR‑16 did not affect Bcl‑2 mRNA expression but downregulated Bcl‑2 protein expression. miR‑16 inhibitor transfection significantly increased Bcl‑2 protein expression and the percentage of apoptotic BM‑MSCs was reduced. The pro‑apoptotic effects of miR‑16 were partially elevated by knocking down of Bcl‑2. Furthermore, it was demonstrated that miR‑16 exerted its pro‑apoptotic effects by activating the mitochondrial pathway of apoptosis via apoptotic protease activating factor‑1/caspase‑9/poly (ADP ribose) polymerase. Taken together, the results indicated that miR‑16 downregulated Bcl‑2 expression and promoted BM‑MSC apoptosis, indicating that therapies targeting miR‑16 may improve the effectiveness of BM‑MSC transplantation therapy.