Up-regulated miR-106b inhibits ox-LDL-induced endothelial cell apoptosis in atherosclerosis

This research aimed to explore the molecular mechanism of microRNA (miR)-106b in cell apoptosis of atherosclerosis (AS). Human aortic endothelial cells (HAECs) were divided into control group, oxidized-low-density lipoproteins (ox-LDL) group, miR-106b NC+ox-LDL group, miR-106b mimics+ox-LDL group, miR-106b mimics+PTEN+ox-LDL group, and miR-106b mimics+empty+ox-LDL group. Real-time fluorescence quantitative polymerase chain reaction, cholecystokinin, TdT-mediated biotinylated nick end-labeling assay, luciferase reporter gene assay, and flow cytometry analysis were performed to determine the morphology, proliferation, and apoptosis in HSECs. Moreover, the levels of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), Bcl-2, p-P13K, and p-AKT in HAECs were detected by western blot. MiR-106b was down-regulated in ox-LDL-induced HAECs. PTEN was the target gene of miR-106b-5p. Overexpression of PTEN inhibited the anti-apoptotic effect of miR-106b. Compared with the control group, the proportion and number of HAECs apoptosis and Bax, caspase-3, and caspase-9 expression in ox-LDL and miR-106b mimics+PTEN+ox-LDL groups were significantly increased (all P<0.05). Moreover, the activity of HAECs and Bcl-2 were decreased significantly (all P<0.05). Overexpression of miR-106b in ox-LDL-induced AS inhibited endothelial cell apoptosis. Furthermore, miR-106b might activate the PI3K/AKT pathway by down-regulating the expression of PTEN in ox-LDL-induced HAECs.

Inhibition of Tumor Angiogenesis by Targeted Induction of Endothelial Cell Apoptosis / 中山大学学报(医学科学版)

Angiogenesis is one of the important pathological characteristics in the development of tumor growth. Hence ,an?ti-angiogenes is has become a hot topic in the field of cancer research. The current strategy for anti-angiogenesis therapy is to restore the angiogenic balance which is broken in the tumor via either block of proangiogenic factorsor application of angiogenic inhibitors. Endogenous angiogenic inhibitors show more promising prospects compared with proangiogenic factor antagonists. However ,the un?derlying mechanisms for the angiogenic inhibitors remain to be thoroughly elucidated. There are two kinds of endogenous angiogenic inhibitors,one is the hydrolyzed fragments of precursor protein,such as plasminogen Kringle 5(K5),angiostatin/kringle 1~4,end?ostatin,etc;the other is cell secreted proteins,such as pigment epithelium-derived factor(PEDF),kallikrein-binding protein (KBP/kallistatin),antithrombin,etc. Here we summarized the research progresses on the biological functions,underlying mecha?nisms of tumor angiogenesis and application prospects of K5,PEDF,and KBP,so as to provide insights into the antiangiogenic ther?apies of tumor in the future.