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1.
Cell Biol Toxicol ; 39(6): 2631-2645, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36715854

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/metabolismo
2.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 32(5): 466-470, 2016 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-29931854

RESUMO

OBJECTIVE: To investigate the electrophysiological effects of ischemia/reperfusion (I/R) on the spontaneous slow response action potentials in guinea-pig left ventricular outflow tract and the effects of antiarrhythmic drugs onI/R. METHODS: The action potentials of pacemaker cells in guinea-pig left ventricular outflow tract were recorded by conventional intracellular microelectrode technique. The influences of ischemia(I) 10 min, reperfusion(R) 2 min, and R 15min on the spontaneous slow response potentials were investigated. The effects of lidocaine, propafenone, amiodarone, verapamil, adenosine, and sodium nitroprusside (SNP) on I/R were also studied. Electrophysiological parameters were examined:velocity of diastolic depolarization(VDD), rate of pacemaker firing(RPF), maximal diastolic potential(MDP), maximal rate of depolarization(Vmax), amplitude of action potential(APA), 50% and 90% of duration of action potential(APD50 and APD90). RESULTS: ①In I 10 min group, the values of VDD, RPF, Vmax and APA were decreased markedly compared with control group (P<0.05, P<0.01).In R 2 min group, VDD and RPF were increased significantly(P<0.01), MDP was increased notably(P<0.05), APD50 and APD90 were shortened significantly compared with I 10 min and control group. Vmax was increased markedly vs control group(P<0.05). APA was decreased notably vs I 10 min group (P<0.05), but was increased markedly vs control group(P<0.05). In R 15 min group, the action potentials recovered gradually to the levels of control group. ② Compared with I 10 min/R 2 min group, 1 µmol/L lidocaine, 10 µmol/L propafenone, 1 µmol/L amiodarone, 1 µmol/L verapamil, 50 µmol/L adenosine, and 10 µmol/L SNP decreased VDD and RPF significantly. CONCLUSIONS: I/R injury can trigger abnormal spontaneous activities of guinea-pig left ventricular outflow tract.The electrophysiological effects of I/R injury on left ventricular outflow tract can be treated by antiarrhythmic drugs.


Assuntos
Potenciais de Ação , Antiarrítmicos/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Traumatismo por Reperfusão , Disfunção Ventricular Esquerda/tratamento farmacológico , Animais , Fenômenos Eletrofisiológicos , Cobaias
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