RESUMO
Emerging reports demonstrated that long non-coding RNAs (lncRNAs) play a role in the pathogenesis and metastasis of cancers. However, the biological functions and underlying mechanisms of LncRNA CEBPA-AS1 in acute myeloid leukemia (AML) remain largely elusive. The level of CEBPA-AS1 was examined in AML clinical tissues and cell lines via fluorescence in situ hybridization (FISH) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In vivo and in vitro functional tests were applied to identify the pro-oncogenic role of CEBPA-AS1 in AML development. The overexpressed CEBPA-AS1 was linked to poor survival in AML patients. Moreover, the relationships among CEBPA-AS1, Zinc Finger Protein X-Linked (ZFX), and miR-24-3p were predicted by bioinformatics and validated by RNA immunoprecipitation (RIP) and luciferase reporter assays. Our findings unveiled that transcription factor ZFX particularly interacted with the promoter of CEBPA-AS1 and activated CEBPA-AS1 transcription. Downregulation of CEBPA-AS1 inhibited the proliferation and invasion while promoted apoptosis of AML cells in in vitro, as well as in vivo, xenograft tumor growth was modified. However, overexpression of CEBPA-AS1 observed the opposite effects. Furthermore, CEBPA-AS1 acted as a competitive endogenous RNA (ceRNA) of miR-24-3p to attenuate the repressive effects of miR-24-3p on its downstream target CTBP2. Taken together, this study emphasized the pro-oncogenic role of CEBPA-AS1 in AML and illustrated its connections with the upstream transcription factor ZFX and the downstream regulative axis miR-24-3p/CTBP2, providing important insights to the cancerogenic process in AML.
Assuntos
Leucemia Mieloide Aguda , MicroRNAs , RNA Longo não Codificante , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação para Cima/genética , Linhagem Celular Tumoral , Hibridização in Situ Fluorescente , Leucemia Mieloide Aguda/genética , Fatores de Transcrição/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Movimento Celular/genética , Oxirredutases do Álcool/genética , Oxirredutases do Álcool/metabolismo , Proteínas Correpressoras/genética , Proteínas Correpressoras/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismoRESUMO
OBJECTIVE: Inflammation and coagulation occur concomitantly in severe pneumonia. The term non-overt disseminated intravascular coagulation (DIC) (pre-DIC state) refers to a state prevalent before the occurrence of overt DIC. It is suggested that initiation of treatment in non-overt DIC leads to better outcome than in overt DIC. The present study aimed at evaluating potential use of soluble P-selectin in diagnosis of pre-DIC state of children with severe pneumonia. METHOD: The laboratory findings (including soluble P-selectin, D-Dimer, platelet count, activated partial prothrombin time, prothrombin time and fibrinogen) of 226 children with severe pneumonia from Jan. 2010 to Jul. 2011 in pediatric intensive care unit (PICU), were analyzed in this prospective cohort study, and the ROC curve was plotted to evaluate the potential role of soluble P-selectin in diagnosis of pre-DIC state. RESULT: A total of 226 patients with severe pneumonia comprised of 75 positive and 151 negative pre-DIC state cases were enrolled. The mean value of soluble P-selectin, D-Dimer, and platelet count were 124.8 (26.9 - 608.3) µg/L, 1.3(0.7 - 16.0) mg/L and 91 (56 - 196)×10(9) for the positive cases, and 63.3 (2.8 - 302.1) µg/L, 0.5 (0.2 - 1.0) mg/L and 231 (120 - 680)×10(9) for the negative cases, respectively. There was a significant difference between the two groups. Coagulatory function in the positive cases, including activated partial prothrombin time, prothrombin time and fibrinogen which were (39.1 ± 3.5) sec, (14.8 ± 2.1) sec and (3.8 ± 0.5) g/L, respectively, were significantly higher than those in the negative cases [(37.2 ± 2.4) sec, (13.0 ± 0.5) sec and (3.3 ± 0.2) g/L] (P < 0.001). The area under ROC curve showed that D-dimer, soluble P-selectin for pre-DIC state had higher diagnostic value. The Optimal Operating Point of soluble P-selectin was determined and interpreted at 94.0 µg/L with a sensitivity of 0.824, a specificity of 0.887, and the Optimal Operating Point of D-dimer was determined and interpreted at 0.7 mg/L with a sensitivity of 0.905, a specificity of 0.867, systematic test of soluble P-selectin and D-dimer had a higher specificity of 0.920, determined at the same time. CONCLUSION: To improve the outcome of patients with DIC, there is a need to establish more useful and easily operative diagnostic criteria for pre-DIC state. Plasma levels of soluble P-selectin will be helpful in this respect. Systematic test of soluble P-selectin and D-dimer may be helpful in reducing misdiagnosis rate.
