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微小RNA-100在人膀胱癌5637细胞中发挥肿瘤抑制作用。

MicroRNA-100 acts as a tumor suppressor in human bladder carcinoma 5637 cells.

作者信息

Oliveira Jaqueline C, Brassesco María S, Morales Andressa G, Pezuk Julia A, Fedatto Paola Fernanda, da Silva Glenda N, Scrideli Carlos A, Tone Luiz G

机构信息

Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil.

出版信息

Asian Pac J Cancer Prev. 2011;12(11):3001-4.

Abstract

Bladder carcinoma is one of the most common tumors in the world and despite the therapy currently available most of the patients relapse. Better understanding of the factors involved in disease pathogenesis would provide insights for the development of more effective strategies in treatment. Recently, differential miRNA expression profiles in bladder urothelial carcinomas identified miR-100 down-regulation and miR-708 up-regulation among the most common alterations, although the possible influence of these miRNAs in the control of basic mechanisms in bladder tumors has not been addressed. In this context, the present study aimed to evaluate the in vitro effects of miR-100 forced expression and miR-708 inhibition in the bladder carcinoma cell line 5637. Our results showed that overexpression of miR-100 significantly inhibited growth when compared to controls at both times tested (72 and 96 hours, p<0.01) with a maximum effect at 72 hours reducing proliferation in 29.6 %. Conversely, no effects on cell growth were observed after inhibition of miR-708. MiR-100 also reduced colony formation capacity of 5637 cells by 24.4%. No alterations in cell cycle progression or apoptosis induction were observed. The effects of miR-100 on growth and clonogenicity capacity in 5637 cells evince a possible role of this miRNA in bladder carcinoma pathogenesis. Further studies are necessary to corroborate our findings and examine the potential use of this microRNA in future therapeutic interventions.

摘要

膀胱癌是世界上最常见的肿瘤之一,尽管目前有多种治疗方法,但大多数患者仍会复发。更好地了解疾病发病机制中涉及的因素将为开发更有效的治疗策略提供思路。最近,在膀胱尿路上皮癌中发现的差异miRNA表达谱显示,miR-100下调和miR-708上调是最常见的变化,尽管这些miRNA在膀胱肿瘤基本机制控制中的可能影响尚未得到研究。在此背景下,本研究旨在评估miR-100强制表达和miR-708抑制对膀胱癌细胞系5637的体外影响。我们的结果表明,与对照组相比,miR-100过表达在两个测试时间点(72小时和96小时,p<0.01)均显著抑制生长,在72小时时效果最佳,使增殖降低29.6%。相反,抑制miR-708后未观察到对细胞生长的影响。miR-100还使5637细胞的集落形成能力降低了24.4%。未观察到细胞周期进程或凋亡诱导的改变。miR-100对5637细胞生长和克隆形成能力的影响表明该miRNA在膀胱癌发病机制中可能发挥作用。需要进一步研究来证实我们的发现,并研究这种 microRNA在未来治疗干预中的潜在用途。

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