Altered MicroRNA expression in cervical carcinomas

Altered MicroRNA expression in cervical carcinomas
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DOI:
10.1158/1078-0432.ccr-07-1231
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发表时间:
2008-05-01
影响因子:
11.5
通讯作者:
Bae, Duk-Soo
Bae, Duk-Soo
中科院分区:
医学1区
文献类型:
--
作者:
Lee, Jeong-Won;Choi, Chel Hun;Bae, Duk-Soo

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目的:MicroRNA(miRNA)是一种长度为18 ~ 25个核苷酸的非编码小RNA,它们调节靶mRNA的稳定性或翻译效率。新出现的证据表明,miRNA可能参与多种人类cancer.Experimental Design的发病机制:在这项研究中,我们分析了miRNA的表达在10个早期浸润性鳞状细胞癌(ISCC)和10个正常宫颈鳞状上皮标本使用TaqMan实时定量PCR阵列方法。结果:共检测到70个基因(68个上调,2个下调)在宫颈癌组织中的表达,与正常宫颈组织相比差异有统计学意义(P < 0.05)。当我们分析31例ISCC中10种最显著的miRNAs表达时,miR-127表达的增加与淋巴结转移显著相关(P = 0.006)。抗miR-199 a寡核苷酸转染宫颈癌细胞抑制细胞生长在体外,这是加强与抗癌剂cisplatin.Conclusions:我们的研究结果表明,miRNA失调可能发挥重要作用,在宫颈鳞状细胞的恶性转化。此外,它们可能提供新的候选靶点,可用于宫颈癌患者的预后和治疗策略。
Purpose: MicroRNAs (miRNA) are small noncoding RNAs that are 18 to 25 nucleotides in length; they regulate the stability or translational efficiency of target mRNAs. Emerging evidence suggests that miRNAs might be involved in the pathogenesis of a variety of human cancers.Experimental Design: In this study, we profiled miRNA expression in 10 early stage invasive squamous cell carcinomas (ISCC) and 10 normal cervical squamous epithelial specimens using Taq Man real-time quantitative PCR array methods. In order to evaluate the role of miR-199a, one of the most significantly overexpressed in ISCCs, we transfected cervical cancer cells (SiHa and ME-180) with anti - miR-199a oligonucleotides and assessed the cell viability.Results: We found 70 genes (68 up-regulated, 2 down-regulated) with significantly different expression in the ISCCs compared with normal samples (P < 0.05). When we analyzed the expression of the 10 most significant miRNAs in 31 ISCCs, increased miR-127 expression was significantly associated with lymph node metastasis (P = 0.006). Transfection of anti miR-199a oligonucleotides to cervical cancer cells suppressed cell growth in vitro, which was potentiated with the anticancer agent cisplatin.Conclusions: Our results show that miRNA deregulation may play an important role in the malignant transformation of cervical squamous cells. In addition, they may offer new candidate targets to be exploited for both prognostic and therapeutic strategies in patients with cervical cancer.