MicroRNA expression variability in human cervical tissues.

MicroRNA expression variability in human cervical tissues.
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DOI:
10.1371/journal.pone.0011780
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发表时间:
2010-07-26
期刊:
影响因子:
3.7
通讯作者:
Santos MA
Santos MA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Pereira PM;Marques JP;Soares AR;Carreto L;Santos MA

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MicroRNAs (miRNAs)是短的(~ 22 nt)非编码调控rna,在转录后水平上控制基因表达。在多种肿瘤中已经发现了miRNA表达的失调,现在很清楚它们有助于癌症的发展和进展。子宫颈癌是全世界妇女中最常见的癌症之一,迫切需要一种非侵入性、快速和有效的方法来诊断这种疾病。我们使用含有成熟miRNA探针的微阵列平台研究了宫颈癌中的miRNA表达谱。我们评估了来自25名不同患者的异质宫颈组织的miRNA表达谱。该组包括19例正常宫颈组织,4例鳞状细胞癌,5例高级别鳞状上皮内病变(HSIL)和9例低级别鳞状上皮内病变(LSIL)。我们观察到miRNA表达的高度变异性,特别是在正常宫颈样本中,这使我们无法获得这种肿瘤类型的独特miRNA表达特征。然而,在解决了观察到的高表达变异性后,在恶性和癌前宫颈组织中发现了失调的mirna。我们还能够识别相关候选mirna的假定靶基因。我们的研究结果表明,miRNA表达在人类样本中表现出自然变异性,这使得miRNA数据分析变得复杂。然而,这种表达噪声可以被过滤,并不妨碍识别在宫颈鳞状细胞恶性转化中起作用的失调mirna。解除调控的mirna突出了新的候选基因靶标,从而更好地理解了这种肿瘤类型发展的分子机制。
MicroRNAs (miRNAs) are short (∼22 nt) non-coding regulatory RNAs that control gene expression at the post-transcriptional level. Deregulation of miRNA expression has been discovered in a wide variety of tumours and it is now clear that they contribute to cancer development and progression. Cervical cancer is one of the most common cancers in women worldwide and there is a strong need for a non-invasive, fast and efficient method to diagnose the disease. We investigated miRNA expression profiles in cervical cancer using a microarray platform containing probes for mature miRNAs. We have evaluated miRNA expression profiles of a heterogeneous set of cervical tissues from 25 different patients. This set included 19 normal cervical tissues, 4 squamous cell carcinoma, 5 high-grade squamous intraepithelial lesion (HSIL) and 9 low-grade squamous intraepithelial lesion (LSIL) samples. We observed high variability in miRNA expression especially among normal cervical samples, which prevented us from obtaining a unique miRNA expression signature for this tumour type. However, deregulated miRNAs were identified in malignant and pre-malignant cervical tissues after tackling the high expression variability observed. We were also able to identify putative target genes of relevant candidate miRNAs. Our results show that miRNA expression shows natural variability among human samples, which complicates miRNA data profiling analysis. However, such expression noise can be filtered and does not prevent the identification of deregulated miRNAs that play a role in the malignant transformation of cervical squamous cells. Deregulated miRNAs highlight new candidate gene targets allowing for a better understanding of the molecular mechanism underlying the development of this tumour type.
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