MicroRNA Expression Variability in Human Cervical Tissues

Abstract

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.

Expression of MiR200a, miR93, Metastasis-related Gene RECK and MMP2/MMP9 in Human Cervical Carcinoma - Relationship with Prognosis

“…In previous research on human cervical cancer, expression of miR-15a, miR-20b, miR-21 and miR-224 is obviously increased in tissue and let-7c, miR-143, miR-199a-5p, miR-203 and miR-145 is reduced (Pereira et al, 2010;Wang et al, 2008). In our study, miRNAs expressions were quantified by using quantitative real-time PCR in which miR-93, miR-200a were up-regulated in cervical carcinoma tissue.…”

Roles of the canonical myomiRs miR-1, -133 and -206 in cell development and disease

“…Additionally, the mature miR isomers are difficult to distinguish by molecular assay and some reports note cross-identification of miR-133b by Taqman mature miR133a specific probe [14] , which is used in many studies. Others [114,117] also make this point, that the different miR assay platforms generate different profiles which may obscure or confuse the identity of observed molecular changes, and at minimum generate apparently different miR profiles of the same tissues or diseases [118,119] . It is essential to accurately determine the specific expression of particular myomiR isomers and their alleles to understand the control processes of particular pathological states.…”

Identification of miR-23a as a novel microRNA normalizer for relative quantification in human uterine cervical tissues

“…The microRNA represents an important new class of regulatory biomolecules that play fundamental global roles in human biology, including development, differentiation, apoptosis, metabolism, viral infection and tumor genesis (Wu et al, 2007;Thomison et al, 2008), suggesting that it very likely to play a key role in the occurrence and development of the HPV-induced cervical cancer. In recent years, differences in the miRNome (defined as the full complement of microRNAs in a genome) have been detected in normal versus pathologic cervical tissues or in the same tissues at different stages of differentiation (Martin et al, 2006;Lui et al, 2007;Thomison et al, 2008;Wang et al, 2009;Hu et al, 2010;Pereira et al, 2010). These differences frequently occur in tumor-specific microRNA signatures, which are very helpful to diagnose the origin of the neoplasia and, sometimes, also specific tumor subtypes.…”