Double strand RNA-guided endogeneous E-cadherin up-regulation induces the apoptosis and inhibits proliferation of breast carcinoma cells in vitro and in vivo

Double strand RNA-guided endogeneous E-cadherin up-regulation induces the apoptosis and inhibits proliferation of breast carcinoma cells in vitro and in vivo
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双链RNA引导内源性E-钙粘蛋白上调诱导体内外乳腺癌细胞凋亡并抑制增殖

DOI:
10.1111/j.1349-7006.2010.01594.x
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发表时间:
2010-08-01
期刊:
影响因子:
5.7
通讯作者:
Zhang Huizhong
Zhang Huizhong
中科院分区:
医学2区
文献类型:
--
作者:
Wei Junxia;Gao Ping;Zhang Huizhong

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e -钙粘蛋白在上皮细胞-细胞粘附和组织结构维持中起着至关重要的作用。E-cadherin表达下调与强侵袭潜能相关,导致包括乳腺癌在内的许多人类癌症预后不良。e -钙粘蛋白的修复可以抑制多种肿瘤细胞的侵袭和转移。已经证明启动子超甲基化导致e -钙粘蛋白的转录下调。在这里,我们利用RNAa技术通过转录调控特异性激活E-cadherin的表达,评估了转染小激活rna (saRNAs)后乳腺癌细胞系的表型变化。我们在体外观察了人乳腺癌细胞凋亡、增殖抑制和迁移减少。动物实验结果表明,与scramble双小RNA (dsRNA)相比,saRNA在体内具有抑制肿瘤生长的作用。该研究为乳腺癌治疗提供了一种新的潜在策略,也证明了saRNA作为一种增强乳腺癌肿瘤抑制基因表达的治疗选择的潜力。(癌症科学2010)。
E-cadherin plays a crucial role in epithelial cell-cell adhesion and in the maintenance of tissue architecture. Down-regulation of E-cadherin expression correlates with a strong invasive potential, resulting in poor prognosis in many human carcinomas, including breast cancer. Restoration of E-cadherin can inhibit cell invasion and metastasis in many types of tumors. It has been demonstrated that promoter hypermethylation causes transcriptional down-regulation of E-cadherin. Here, using an RNAa technique specifically activating the expression of E-cadherin through transcriptional regulation, we assessed the phenotype changes of a breast carcinoma cell line with transfection of small-activating RNAs (saRNAs). We observed cell apoptosis, proliferation inhibition and reduction in human breast cancer migration in vitro. Animal experiment results showed that saRNA could inhibit tumor growth in vivo compared with scramble double-small RNA (dsRNA).This study provides a new potential strategy for breast cancer therapy, and also demonstrates the potential for saRNA as a therapeutic option for enhancing tumor suppressor gene expression in breast cancer. (Cancer Sci 2010).