Aim: We evaluated the incidence, clinicopathological features, prognostic factors and survival of gastric cancer (GC) with bone metastasis in a single large cancer center in China. Patients & methods: Patients with bone metastasis of GC were retrospectively analyzed. Overall survival was estimated using the Kaplan–Meier method. Clinicopathological factors, which were associated with prognostic factors for survival, were evaluated. Results: The incidence of bone metastasis was 11.3% for metastatic GC patients. Median overall survival time was 6.5 months. Multivariate analysis revealed two independent poor prognostic factors: Eastern Cooperative Oncology Group ≥2 (p = 0.023) and lack of palliative chemotherapy (p = 0.018). Conclusion: The incidence of bone metastasis from metastatic GC was underestimated. The prognosis of GC with bone metastasis was poor.
Recent lentiviral-based microRNA (miRNA) library screening has identified miRNA-7 (miR-7) as an anti‑angiogenic miRNA in human umbilical vein endothelial cells (HUVECs). However, the underlying mechanism of miR-7 in the suppression of angiogenesis remains largely unknown. In the present study, we report that miR-7 inhibition promoted angiogenesis by upregulating vascular endothelial growth factor (VEGF) and directly targeting Krüppel-like factor 4 (KLF4). Downregulation of miR-7 promoted tube formation of HUVECs, accompanied by upregulation of mRNA and protein levels of both VEGF and KLF4. miR-7 directly targeted KLF4 as demonstrated by luciferase reporter assay and miR-7 mimics decreased KLF4. Furthermore, bioinformatic analysis revealed the presence of multiple DNA-binding elements of KLF4 in the VEGF promoter. Chromatin immunoprecipitation (ChIP) demonstrated that the KLF4 antibody specifically pulled down the VEGF promoter in the HUVECs. Furthermore, ectopic overexpression of KLF4 induced VEGF mRNA and protein levels. In addition, KLF4 silencing inhibited the angiogenesis induced by the miR-7 inhibitor in the HUVECs. Our results demonstrated that KLF4 is a direct target of miR-7 and a transcription activator of VEGF. These findings indicate that the miR-7-KLF4-VEGF signaling axis plays an important role in the regulation of angiogenesis in HUVECs, suggesting that miR-7 is a potential agent for the development of anti-angiogenic therapeutics in vascular diseases and solid tumors.
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