RESUMEN
Background: CircZNF609 (cZNF609) is previously revealed as an essential mediator in oxidative stress. This paper determined the role of cZNF609 in skin oxidative damage to evaluate its importance in pressure ulcer.Methods: HaCaT cells treated by H2O2 were considered as a cell model of pressure ulcer. The role of cZNF609 in the model was checked by conducting CCK-8 assay, FITC-PI double-staining, ROS detection and Western blot. The downstream gene and signalling of cZNF609 were studied by utilizing qRT-PCR and Western blot.Results: HaCaT cells were remarkably damaged by H2O2, as evidenced by the viability loss, apoptosis and ROS generation. It was coupled with the elevated expression of p53, p16, Bax and the activated forms of caspase-3 and PARP. Meanwhile, cZNF609 was high-expressed in response to H2O2. The oxidative stress driven by H2O2 was alleviated by transfection with cZNF609 specific siRNA. Further, the anti-antioxidant impacts of cZNF609 silence were impeded by miR-145 silence. The inhibition of JNK and p38MAPK pathways induced by cZNF609 silence was impeded by miR-145 silence.Conclusion: The protective function of cZNF609 silence in H2O2-injured HaCaT cells was revealed in vitro. Silence of cZNF609 exhibited its impact possibly through regulating miR-145, and JNK and p38MAPK pathways.
Asunto(s)
Antioxidantes/farmacología , Queratinocitos/metabolismo , Sistema de Señalización de MAP Quinasas , Estrés Oxidativo , Úlcera por Presión/metabolismo , ARN Circular/metabolismo , Piel/metabolismo , Línea Celular , Humanos , Peróxido de Hidrógeno/farmacología , Queratinocitos/patología , MicroARNs/metabolismo , Úlcera por Presión/patología , Piel/patologíaRESUMEN
Luteolin is a representative of natural flavonoid that has anti-tumour properties. This study designed to check its impact on breast cancer and the underlying mechanisms. MDA-MB-453 and MCF-7 cells were administrated with luteolin and the following techniques were carried out: CCK-8 assay, FITC-PI double-staining and Western blot. qRT-PCR analysis was utilized to see the effects of luteolin on miR-203 expression. Besides, miR-203 expression was silenced by transfection with specific inhibitor. Luteolin remarkably declined MDA-MB-453 and MCF-7 cells viability and accelerated apoptosis which accompanied by Bax up-regulation, Bcl-2 down-regulation and Caspase-3 cleavage. Also, luteolin impeded TGFß1-induced EMT, as evidenced by the decreased levels of Vimentin, Zeb1 and N-cadherin, as well as the increased level of E-cadherin. miR-203 was highly expressed in 22 pair of breast cancer tissues than the matched paracancerous tissues. Luteolin could elevate miR-203 level. Besides, luteolin's anti-tumour effects were partially eliminated by miR-203 silence. Further, luteolin inhibited Ras/Raf/MEK/ERK signalling, while the inhibitory effects were flattened by miR-203 silence. Luteolin significantly reduced breast cancer cells growth and EMT. Luteolin exerted its anti-tumour effects possibly involved the elevated expression of miR-203 and the inhibited Ras/Raf/MEK/ERK signalling.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/patología , Luteolina/farmacología , MicroARNs/genética , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Células MCF-7 , Quinasas raf/metabolismo , Proteínas ras/metabolismoRESUMEN
BACKGROUND: Several recent genome-wide association studies tried to explore associations between LOC643714 polymorphisms and breast cancer (BC). However, the results of these studies were inconsistent. The purpose of this meta-analysis was to better analyze the effects of LOC643714 polymorphisms on individual susceptibility to BC in a larger pooled population. MATERIALS AND METHODS: PubMed, Web of Science, and Embase were searched for eligible studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of associations. RESULTS: In total, 42 studies with 231,191 subjects were analyzed. Significant associations with BC were observed for rs3803662 (dominant comparison: OR, 0.89; 95% CI, 0.84-0.95; P = .0008; recessive comparison: OR, 1.17; 95% CI, 1.07-1.28; P = .0004; over-dominant comparison: OR, 1.07; 95% CI, 1.02-1.11; P = .002; allele comparison: OR, 0.90; 95% CI, 0.86-0.95; P = .0002), rs8051542 (dominant comparison: OR, 0.87; 95% CI, 0.83-0.91; P < .0001; recessive comparison: OR, 1.19; 95% CI, 1.11-1.28; P < .0001; over-dominant comparison: OR, 1.07; 95% CI, 1.02-1.11; P = .004; allele comparison: OR, 0.89; 95% CI, 0.86-0.91; P < .0001), and rs12922061 (dominant comparison: OR, 0.83; 95% CI, 0.73-0.93; P = .002; over-dominant comparison: OR, 1.43; 95% CI, 1.27-1.61; P < .0001) polymorphisms in the overall population. Further subgroup analyses yielded similar positive results for rs3803662 and rs8051542 polymorphisms in Asians, Caucasians, and Africans, for rs12443621 polymorphism in Caucasians, and for rs12922061 polymorphism in Asians. CONCLUSIONS: Our findings suggested that LOC643714 rs3803662, rs8051542, rs12443621, and rs12922061 polymorphisms were all significantly associated with BC in certain populations.