Bombesin-like peptides are essential autocrine growth factors for many small cell carcinomas (SCCas) of the lung. Herein, we demonstrate that these malignant pulmonary neuroendocrine cells express low levels of the cell surface metalloendopeptidase CD10/neutral endopeptidase 24.11 (CD10/NEP, common acute lymphoblastic leukemia antigen)

miR-126 is an endothelial-specific microRNA essential for governing vascular integrity and angiogenesis. Its role in tumor angiogenesis of gastric cancer (GC) is unclear. This study aimed at determining the role of miR-126 in GC angiogenesis. Down-regulation of miR-126 was found to inversely correlate with an increased microvessel density (MVD) and vascular endothelial growth factor A (VEGF-A) expression in gastric cancer tissues. Bioinformatics analysis and luciferase reporter assay revealed that miR-126 directly targeted the 3′-untranslated region (3′-UTR) of VEGF-A mRNA. In addition, the restoration of miR-126 expression by lentivirus-miR-126 (Lenti-miR-126) transfection obviously reduced the expression of VEGF-A and the activition of its downstream genes, Akt, mTOR and Erk1/2 in gastric cancer cell lines SGC-7901, MKN-28 and MKN-45. In contrast, the down-regulation of miR-126 expression by lentivirus-anti-miR-126 (Lenti-anti-miR-126) transfection obviously up-regulated the expression of VEGF-A and its downstream signaling pathways. In vivo xenograft mice model experiments clarified the down-regulation of VEGF-A and MVD as well as inhibition of tumor growth by up-regulation of miR-126. Overall, the results from our study suggested that miR-126 could suppress tumor growth and tumor angiogenesis of GC through VEGF-A signaling, and it is a novel potential therapeutic target for GC.

p21Ras mediates mitogenic responses and also renders cells susceptible to apoptosis after inhibition of protein kinase C (PKC) activity. Ras-induced apoptosis can be blocked by the proto-oncogene bcl-2, but the biochemical or functional nature of Bcl-2 regulation of Ras-induced apoptosis is not understood. We demonstrate that Bcl-2 and p21Ras molecules can be co-immunoprecipitated in Jurkat cells. The level of this association is enhanced when an apoptotic stimulus (inhibition of PKC activity) is delivered. Bcl-2/p21Ras association is coincident with new phosphorylation of the Bcl-2 protein. Inhibition of this phosphorylation prevents protection from apoptosis by Bcl-2, providing a functional correlation to the phosphorylation event. The Bcl-2/p21 Ras association cannot be competed by exogenous glutathione S-transferase-Ras fusion protein, suggesting that the endogenous complex may be formed before cell lysis. These results provide a possible mechanism of regulation of Ras-induced apoptosis by Bcl-2.