MicroRNA analysis in human papillomavirus (HPV)-associated cervical neoplasia and cancer

Gardiner, Amy S.; McBee, William C.; Edwards, Robert P.; Austin, Marshall; Lesnock, Jamie; Bhargava, Rohit; Guido, Richard S.; Khan, Saleem A.

doi:10.1186/1750-9378-5-s1-a55

Cited by 10 publications

(13 citation statements)

References 92 publications

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“…Among the literature-based validated targets, miR-21 a microRNA largely discussed in the literature has been found upregulated, similarly to the majority of previous studies (32,33). miR-21 has been shown as an oncogene capable to regulate genes as Bcl-2 (34).…”

Section: Discussionsupporting

confidence: 58%

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microRNA Portraits in Human Vulvar Carcinoma

Maia

Lavorato-Rocha

Rodrigues

et al. 2013

Cancer Prevention Research

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Unregulated expression of microRNAs is well known and has already been demonstrated in many tumor types. However, in vulvar carcinoma this field has been unknown territory. Our study characterizes microRNA in vulvar tumors through an expression profile of 754 miRNAs, relating this with clinical and anatomopathologic data, and presence of HPV infection. Twenty HPV-negative and 20 HPV-positive samples, genotyped for high-risk HPVs (HPV16, 18, 31, 33) and a pool of seven normal vulvar skin samples were used for the identification of differentially expressed miRNAs by TLDA Quantitative Real Time PCR (qRT-PCR). Twenty-five differentially expressed microRNAs between HPV-positive and HPV-negative groups and 79 differentially expressed on the tumor compared with normal samples were obtained. A network between microRNA expression profiles and putative target mRNAs predicted by target prediction algorithms and previously demonstrated as relevant in vulvar carcinomas, such as TP53, RB, PTEN, and EGFR was constructed. Downregulation of both miR-223-5p and miR-19-b1-5p were correlated with the presence of lymph node metastasis; downregulation of miR-100-3p and miR-19-b1-5p were correlated with presence of vascular invasion; overexpression of miR-519b and miR-133a were associated with advanced FIGO staging. In conclusion, our study demonstrates that microRNAs may be clinically important in vulvar carcinomas and our findings may help for further studies on functional implications of miRNA deregulation in this type of cancer. Cancer Prev Res; 6(11); 1231-41. Ó2013 AACR.

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Section: Discussionsupporting

confidence: 58%

“…Of paramount importance, miR-21 and miR-106b are located near HPV integration sites, which indicate that these microRNAs may have implications in vulvar cancer, a tumor in which HPV has already been shown as having relevant clinical importance (33,34). miR-106 was found upregulated among our HPV-positive samples.…”

Section: Discussionmentioning

confidence: 65%

microRNA Portraits in Human Vulvar Carcinoma

Maia

Lavorato-Rocha

Rodrigues

et al. 2013

Cancer Prevention Research

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“…In HPV‐induced cancer, numerous miRNAs have been identified as oncomiRs. Similarly, miRNAs including let‐7 family, miR‐7, miR‐17‐5p, miR‐125, miR‐218 and miR‐433 have been reported to function as tumour suppressors . In HPV‐induced cancers, the expression of E6 and E7 has been linked to aberrant expression of miRNAs leading to alteration of p53 and pRB pathways and associated with carcinogenic transformation …”

Section: Introductionmentioning

confidence: 99%

Differential expression of microRNAs in bovine papillomavirus type 1 transformed equine cells

Terron‐Canedo

Weir

Nicolson

et al. 2016

Vet Comparative Oncology

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Bovine papillomavirus (BPV) types 1 and 2 play an important role in the pathogenesis of equine sarcoids (ES), the most common cutaneous tumour affecting horses. MicroRNAs (miRNAs), small non-coding RNAs that regulate essential biological and cellular processes, have been found dysregulated in a wide range of tumours. The aim of this study was to identify miRNAs associated with ES. Differential expression of miRNAs was assessed in control equine fibroblasts (EqPalFs) and EqPalFs transformed with the BPV-1 genome (S6-2 cells). Using a commercially available miRNA microarray, 492 mature miRNAs were interrogated. In total, 206 mature miRNAs were differentially expressed in EqPalFs compared with S6-2 cells. Aberrant expression of these miRNAs in S6-2 cells can be attributed to the presence of BPV-1 genomes. Furthermore, we confirm the presence of 124 miRNAs previously computationally predicted in the horse. Our data supports the involvement of miRNAs in the pathogenesis of ES.2

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“…Consistent with this speculation, in vivo analysis revealed that patients who carry the rs1131445 C allele had a higher serum IL-16 than non-carriers, which led to an elevated serum IL-16 of patients compared to healthy controls. The upregulation of miR-135b has been found in cervical cancer [42] , which could inhibit the expression of IL-16 by targeting its 3′-UTR. The rs1131445 C allele impairs the binding of miR-135b to the target and leads to higher constitutive expression of IL-16 and subsequent release to serum.…”

Section: Discussionmentioning

confidence: 99%

Genetic Variants in microRNA Target Sites of 37 Selected Cancer-Related Genes and the Risk of Cervical Cancer

et al. 2014

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ObjectivesSingle nucleotide polymorphisms (SNPs) in putative microRNA binding sites (miRSNPs) modulate cancer susceptibility via affecting miRNA binding. Here, we sought to investigate the association between miRSNPs and cervical cancer risk.MethodsWe first genotyped 41 miRSNPs of 37 cancer-related genes in 338 patients and 334 controls (Study 1), and replicated the significant associations in 502 patients and 600 controls (Study 2). We tested the effects of miRSNPs on microRNA-mRNA interaction by luciferase reporter assay.ResultsFive SNPs displayed notable association with cervical cancer risk in Study 1. Only IL-16 rs1131445 maintained a significant association with cervical cancer (CT/CC vs. TT, adjusted OR = 1.51, P = 0.001) in Study 2. This association was more evident in the combined data of two studies (adjusted OR = 1.49, P = 0.00007). We also found that miR-135b mimics interacted with IL-16 3′-UTR to reduce gene expression and that the rs1131445 T to C substitution within the putative binding site impaired the interaction of miR-135b with IL-16 3′-UTR. An ELISA indicated that the serum IL-16 of patients with cervical cancer was elevated (vs. controls, P = 0.001) and correlated with the rs1131445 genotype. Patients who carried the rs1131445 C allele had higher serum IL-16 than non-carriers (P<0.001).ConclusionsThese results support our hypothesis that miRSNPs constitute a susceptibility factor for cervical cancers. rs1131445 affects IL-16 expression by interfering with the suppressive function of miR135b and this variant is significantly associated with cervical cancer risk.

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MicroRNA analysis in human papillomavirus (HPV)-associated cervical neoplasia and cancer

Abstract: Gardiner et al.: MicroRNA analysis in human papillomavirus (HPV)-associated cervical neoplasia and cancer. Infectious Agents and Cancer 2010 5(Suppl 1):A55.

Cited by 10 publications

References 92 publications

microRNA Portraits in Human Vulvar Carcinoma

microRNA Portraits in Human Vulvar Carcinoma

Differential expression of microRNAs in bovine papillomavirus type 1 transformed equine cells

Genetic Variants in microRNA Target Sites of 37 Selected Cancer-Related Genes and the Risk of Cervical Cancer

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