Hypoxia promotes the expression of Von Willebrand factor in breast cancer cells by up-regulating the transcription factor YY1 and down-regulating the hsa-miR-424.

Von Willebrand factor (VWF), a large glycoprotein with hemostatic properties, is mainly synthesized by megakaryocytes and endothelial cells (ECs). In recent years, studies have found that tumor cells also can produce VWF de novo. Tumor growth is usually accompanied by hypoxic environment, and whether hypoxia will influence von Willebrand factor production in tumor cells is still unknown. In this research, we demonstrated that hypoxia could induce the production of VWF in breast cancer cells (MCF-7 and MDA-MB-231 cell lines), and promoted cell migration as well as angiogenesis. Notably, VWF is a key factor for hypoxia to promote breast cancer cell migration and angiogenesis, and knocking down VWF can attenuate the effects of hypoxia. Further study was conducted on the molecular mechanism to clarify why hypoxia can promote VWF synthesis in breast cancer cells. We found that Yin-Yang 1 (YY1, a transcription factor) had a binding site to the promoter region of VWF, and acted as a transcriptional activator of VWF. Meanwhile, hsa-miR-424 inhibited VWF production by associating with the 3'-UTR of VWF mRNA. Here, we proved that hypoxia up-regulated the transcription factor YY1 and down-regulated hsa-miR-424 to increase the expression level of VWF. Additionally, knockdown of transcription factor YY1 and transfection of hsa-miR-424 mimics had a synergistic effect in reducing hypoxia-induced VWF production of breast cancer cells, cell migration and angiogenesis in vitro.

The effect of older-person centered and integrated health management model on multiple lifestyle behaviors: A randomized controlled trial from China.

OBJECTIVE: To investigate the effectiveness of the older-centered Integrated Health Management Model Project (OPCHMP) for multiple lifestyle behaviours in the elderly. METHODS: A 2-arm, parallel, randomized controlled trial was conducted in Nanjing. The elderly were recruited from multiple community health service centres. The intervention group was intervened and received a personalized, 2-year OPCHMP. The control group only received usual care. Adherence to healthy lifestyle behaviours (ATHLBS) is the primary outcome, obtained through a self-reported composite health behaviour score. The secondary outcomes were health indicators. General estimating equation models were performed to analyse longitudinal dichotomous data and continuous data. RESULTS: 637 (intervention = 323; control = 314) participants were included in the study. The participants mean age was 70.53 ±â€¯6.07 years. Significant ATHLBS correction was achieved after 24-month follow-up in the intervention group, comparing to controls. And the intervention group reported significantly better health indicators. CONCLUSION: OPCHMP had positive effect on multiple lifestyle habits in elderly population, which is very encouraging.