摘要：
Retinoblastoma (RB) is commonly-seen cancer in children. The p53 pathway dysfunction, which can lead to elevated MDM2 or MDM4 (p53 antagonists) protein expression, is frequently observed in almost all human cancers, including RB. The present study attempted to investigate the underlying mechanism from the perspective of non-coding RNA regulation. Here, we demonstrated that p53 and miR-129 were positively correlated with each other in RB. miR-129 directly targeted MDM2/4 to inhibit expression, therefore counteracting MDM2/4-mediated p53 signaling suppression and modulating RB cell proliferation and apoptosis. Moreover, p53 could activate the transcription of miR-129 via binding to the miR-129 promoter region, therefore forming a regulatory loop with MDM2/4 to affect RB progression. Altogether, the p53/miR-129/MDM2/4/p53 regulatory loop can modulate RB cell growth. We provide a solid experimental basis for developing novel therapies for RB.
摘要：
Objective To observe the effects and possible mechanism of Ziyin Mingmu Pills (滋阴明目丸) on retinal pigment epithelial (RPE) cells after light injury. Methods A total of 60 SD rats were divided into Ziyin Mingmu Pills low,medium and high dose groups and a blank group,with 15 rats in each group. The groups of different Ziyin Mingmu Pills dosages were respectively administered with the suspension of Ziyin Mingmu Pills at a concentration of 0.39,0.78,and 1.56 g /ml. The gavage volume was 34 ml /(kg·d),and the blank group was given 34 ml /(kg·d) of normal saline for gavage,each group was administered for 7 days. The drug-containing serum was prepared in the end of the gavage,and the concentration of the drug-containing serum in the subsequent experiment was screened by the MTT method. The selected cells for experiment were divided into a blank group (without drugcontaining serum),serum group (with drug-containing serum),model group (light damage modeling,no drug-containing serum),and Chinese medicine group (light damage modeling with drug-containing serum). After 24 hours of culture,the in vitro RPE cell light damage models of model group and the Chinese medicine group were established. The apoptosis rate of each group was measured,and the expression of caspase-1,caspase-3 and mRNA were measured. Results The medium dose serum was the optimal dose,and it was used in subsequent experiments. Compared with the blank group,the apoptosis rate,expression of Caspase-1 and Caspase-3 protein and mRNA in serum group were not statistically significant (P > 0.05). The apoptosis rate,Caspase-1 and Caspase-3 protein and mRNA expression in the model group increased significantly (P < 0.05). Compared with the model group,the apoptosis rate,Caspase-1 and Caspase-3 protein and mRNA expression in the Chinese medicine group were significantly decreased (P < 0.05). Conclusion Ziyin Mingmu Pills can effectively inhibit the apoptosis of RPE cells after light injury. The mechanism may be related to the inhibition of the expression of Caspase-1,Caspase-3 protein and its mRNA.
