Diabetic foot ulcers (DFUs) are caused by impairments in peripheral blood vessel angiogenesis and represent a great clinical challenge. Although various innovative techniques and drugs have been developed for treating DFUs, therapeutic outcomes remain unsatisfactory. Using the GEO database, we obtained transcriptomic microarray data for DFUs and control wounds and detected a significant downregulation of epidermal growth factor receptor (EGFR) in DFUs. We cultured human umbilical vein endothelial cells (HUVECs) and noted downregulated EGFR expression following high-glucose exposure in vitro. Further, we observed decreased HUVEC proliferation and migration and increased apoptosis after shRNA-mediated EGFR silencing in these cells. In mice, EGFR inhibition via focal EGFR-shRNA injection delayed wound healing. Target prediction analysis followed by dual-luciferase reporter assays indicated that microRNA-133b (miR-133b) is a putative upstream regulator of EGFR expression. Increased miR-133b expression was observed in both glucose-treated HUVECs and wounds from diabetes patients, but no such change was observed in controls. miR-133b suppression enhanced the proliferation and angiogenic potential of cultured HUVECs and also accelerated wound healing. Although angiogenesis is not the sole mechanism affected in DFU, these findings suggest that the miR-133b-induced downregulation of EGFR may contribute to delayed wound healing in diabetes. Hence, miR-133b inhibition may be a useful strategy for treating diabetic wounds.
Osteosarcoma is among the most malignant types of tumor worldwide and has become a leading contributor to tumor incidence, particularly in adolescents. Resistance to conventional treatment and the complexity of osteosarcoma tumorigenesis has resulted in high mortality rates. MicroRNAs are a class of noncoding RNAs, which regulate numerous biological processes. However, the involvement of miR-643 in osteosarcoma remains to be elucidated. In the present study, reverse transcription-quantitative polymerase chain reaction, luciferase reporter assay, invasion assay, viability assay, western blot analysis and in vivo implantation were performed to analyze the action of miR-643 in osteosarcoma. The results demonstrated that miR-643 inhibited the progression of osteosarcoma and acted as a potential tumor suppressor. The expression of miR-643 was downregulated in osteosarcoma tissues and cell lines. In addition, miR-643 transfection significantly impaired the proliferation and invasion of osteosarcoma cells. The present study also identified Zinc finger E-box-binding homeobox 1 (ZEB1) as a direct target of miR-643, and the ectopic expression of ZEB1 counteracted the effect of miR-643 transfection. A significant inverse correlation was also found between the expression of miR-643 and ZEB1. A low expression of miR-643 or a high expression of ZEB1 was associated with poor patient survival rates. The results of the present study suggested that the decreased expression of miR-643 may be involved in the mechanism underlying the development of osteosarcoma. The intricate interactions between miR-643 and ZEB1 may serve as a potential therapeutic target in osteosarcoma oncogenesis.
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The association between height and risk of hip fracture has been investigated in several studies, but the evidence is inconclusive. We therefore conducted this meta-analysis of prospective cohort studies to explore whether an association exists between height and risk of hip fracture. We searched PubMed and EMBASE, Web of Science, and the Cochrane Library for studies of height and risk of hip fracture up to February 16, 2016. The random-effects model was used to combine results from individual studies. Seven prospective cohort studies, with 7,478 incident hip fracture cases and 907,913 participants, were included for analysis. The pooled relative risk (RR) was 1.65 (95% confidence interval (CI): 1.26–2.16) comparing the highest with the lowest category of height. Result from dose-response analysis suggested a linear association between height and hip fracture risk (P-nonlinearity = 0.0378). The present evidence suggests that height is positively associated with increased risk of hip fracture. Further well-designed cohort studies are needed to confirm the present findings in other ethnicities.
Circular RNAs (circ RNAs) have been found to play an important role in cancer development. However, the role of circRAB3IP in osteosarcoma (OS) is unclear.In the present study, We found that circRAB3IP was highly expressed in OS tissues and OS cells. High levels of circRAB3IP was correlated with advanced TNM stage, distant metastasis. CircRAB3IP knockdown inhibited cell proliferation, migration, and invasion. Moreover, circRAB3IP directly binds to miR-580-3p. TWIST1 is directly targeted by miR-580-3p. We also demonstrated that circRAB3IP act as the sponge of miR-580-3p to promote TWIST1 expression. CircRAB3IP promotes OS cells proliferation, migration, and invasion through modulating miR-580-3p/TWIST1 axis. Moreover, circRAB3IP facilitated tumor formation in vivo. Our findings suggested that circRAB3IP acts as an oncogene in OS by regulating miR-580-3p/TWIST1 axis.
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