ABSTRACT
Abstract Objective: Long Non-Coding RNAs (LncRNAs) act as an indispensable role in cancer development. The study aimed to investigate the role and mechanism of lncRNA Small Nucleolar RNA Host Gene 1 (SNHG1) in Bladder Cancer (BC) progression. Method: The expression, prognostic value, diagnostic value, and correlation of SNHG1, Enhancer of Zeste 2 polycomb repressive complex 2 subunit (EZH2), and Kruppel Like Factor 2 (KLF2) were analyzed through bioinformatics analysis. The expression was also validated in BC tissues and cell lines. Besides, their regulation and binding were tested via qPCR, Western blot, Dual-Luciferase Reporter Assay (DLRA), Argonaute RISC catalytic component 2-RNA Immunoprecipitation (AGO2-RIP), and Chromatin Immunoprecipitation (ChIP). A xenograft model in nude mice was also established. Results: SNHG1 was significantly overexpressed in BC tissues and cells. Importantly, SNHG1 was associated with poor survival, and ROC curves revealed high diagnostic values. Moreover, by CCK8, wound healing, transwell, and Western blot analysis, SNHG1 knockdown significantly inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition of BC cells. Additionally, in vivo experiments showed that silencing SNHG1 hindered tumorigenesis and tumor growth. Regarding mechanism, the results of AGO2-RIP, ChIP or DLRA showed that SNHG1 played different roles at diverse subcellular sites. In the cytoplasm, SNHG1 acted as a competing endogenous RNA for miR-137-3p to promote EZH2 expression. In the nucleus, SNHG1 could interact with EZH2 to inhibit KLF2 transcription. Conclusion: Our study elucidated that SNHG1 formed a regulatory network and played an oncogenic role in BC, which provided a novel therapeutic target for BC treatment.
ABSTRACT
Unlike adult mammalian heart, zebrafish heart has a remarkable capacity to regenerate after injury. Previous study has shown Notch signaling activation in the endocardium is essential for regeneration of the myocardium and this activation is mediated by hemodynamic alteration after injury, however, the molecular mechanism has not been fully explored. In this study we demonstrated that blood flow change could be perceived and transmitted in a primary cilia dependent manner to control the hemodynamic responsive klf2 gene expression and subsequent activation of Notch signaling in the endocardium. First we showed that both homologues of human gene KLF2 in zebrafish, klf2a and klf2b, could respond to hemodynamic alteration and both were required for Notch signaling activation and heart regeneration. Further experiments indicated that the upregulation of klf2 gene expression was mediated by endocardial primary cilia. Overall, our findings reveal a novel aspect of mechanical shear stress signal in activating Notch pathway and regulating cardiac regeneration.
ABSTRACT
Unlike adult mammalian heart, zebrafish heart has a remarkable capacity to regenerate after injury. Previous study has shown Notch signaling activation in the endocardium is essential for regeneration of the myocardium and this activation is mediated by hemodynamic alteration after injury, however, the molecular mechanism has not been fully explored. In this study we demonstrated that blood flow change could be perceived and transmitted in a primary cilia dependent manner to control the hemodynamic responsive klf2 gene expression and subsequent activation of Notch signaling in the endocardium. First we showed that both homologues of human gene KLF2 in zebrafish, klf2a and klf2b, could respond to hemodynamic alteration and both were required for Notch signaling activation and heart regeneration. Further experiments indicated that the upregulation of klf2 gene expression was mediated by endocardial primary cilia. Overall, our findings reveal a novel aspect of mechanical shear stress signal in activating Notch pathway and regulating cardiac regeneration.
ABSTRACT
Objective To investigate the expressions of KLF2 mRNA and KLF4 mRNA in the acute lung injury (ALl) rats induced by lipopolysaccharide (LPS),and to analyze the correlation between KLF2,KLF4 and ALI.Methods A total of 100 SD rats were randomly divided into 2 groups:normal control group and LPS treated group,then the latter group was randomly further divided into 3 subgroups as per the serum and lung tissue samples taken separately at 2,4 and 24h after modeling.The ALI model was made by injecting 5mg/kg LPS into tail vein.The pathological changes of lung tissue were observed in each group,and the expressions of KLF2,KLF4 mRNA in serum and lung tissue were detected by RT-PCR.The data of laboratory findings were analyzed with SPSS 17.0 software for statistical analysis.Results The histopathological changes showed the most obvious damage of lung tissue occurred at 4 hours after modeling.The expressions of KLF2 mRNA and KLF4 mRNA in the lung tissue and serum of control group were significantly higher compared to LPS treated subgroups (P ＜0.01).The expression of KLF2 mRNA in LPS treated subgroup at 2 hours was lower than that in LPS subgroups at 4 hours and 24 hours (P ＜ 0.01),while the expression of KLF4 mRNA in LPS treated subgroup at 4 hours was lower than that in LPS treated subgroups at 2 hours and 24 hours (P ＜ 0.01).Conclusions The expression of KLF2 mRNA was occurred earlier than the pathological changes in acute lung injury,while the expression of KLF4 was emerged synchronously,and both KLF2 and KLF4 could be used as candidates of predictive and diagnostics molecular markers of ALI.