RNA Biology Laboratory, Department of Biology and CESAM, University of Aveiro, Aveiro, Portugal.
PLoS One. 2010 Jul 26;5(7):e11780. doi: 10.1371/journal.pone.0011780.
MicroRNAs (miRNAs) are short (approximately 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.
微小 RNA（miRNAs）是短（约 22 个核苷酸）的非编码调控 RNA，可在转录后水平控制基因表达。miRNA 表达的失调已在多种肿瘤中被发现，现在清楚的是，它们有助于癌症的发生和发展。宫颈癌是全球女性中最常见的癌症之一，因此强烈需要一种非侵入性、快速和有效的方法来诊断这种疾病。我们使用含有成熟 miRNA 探针的微阵列平台来研究宫颈癌中的 miRNA 表达谱。我们评估了来自 25 位不同患者的异质性宫颈组织的 miRNA 表达谱。该组包括 19 个正常宫颈组织、4 个鳞状细胞癌、5 个高级别鳞状上皮内病变（HSIL）和 9 个低级别鳞状上皮内病变（LSIL）样本。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，这使得我们无法为这种肿瘤类型获得独特的 miRNA 表达特征。然而，在处理观察到的高表达变异性后，在恶性和癌前宫颈组织中鉴定出了失调的 miRNA。我们还能够鉴定出相关候选 miRNA 的潜在靶基因。我们的结果表明，miRNA 表达在人类样本中存在自然变异性，这使得 miRNA 数据谱分析复杂化。然而，这种表达噪声可以被过滤，并且不会阻止鉴定在宫颈鳞状细胞恶性转化中起作用的失调 miRNA。失调的 miRNA 突出了新的候选基因靶标，使我们能够更好地理解这种肿瘤类型发生的分子机制。
