Genetic polymorphisms and microRNAs: new direction in molecular epidemiology of solid cancer

Slabý, Ondřej; Vašků, Julie Bienertová; Svoboda, Marek; Vyzula, Rostislav

doi:10.1111/j.1582-4934.2011.01359.x

Cited by 108 publications

(77 citation statements)

References 81 publications

(129 reference statements)

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“…To the best of our knowledge, the present study is the first combined clinical and cell functional study of the association between rs11614913 SNP and susceptibility to ovarian cancer. It is widely accepted that gene variants located in pri-and pre-miRNA regions may influence the biological functions of miRNAs and eventually lead to alterations in disease incidence (32). Considering this, various studies have investigated the application of pri-and pre-miRNA polymorphisms as predictors of cancer risk (29,31,33).…”

Section: Discussionmentioning

confidence: 99%

Association between the rs11614913 variant of miRNA-196a-2 and the risk of epithelial ovarian cancer

Song

Zhao

et al. 2015

Oncology Letters

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Abstract. Polymorphisms in microRNA (miR) genes and their target sites are a distinct classification of variation in the human genome, which are rapidly being identified and investigated in human cancer. A polymorphism in the miR-196a-2 locus has demonstrated significant associations with various types of cancer, including lung, breast, esophageal and gastric tumors. However, miR-196a-2 has not been fully explored in ovarian cancer, which shares similar biological characteristics with other types of cancer. Therefore, the present study aimed to elucidate the association between a single nucleotide polymorphism (SNP) in the mature sequence of miR-196a-2 (rs11614913, T/C) and the clinical features of 479 Chinese patients with epithelial ovarian cancer (EOC). In addition, the biological significance of this polymorphism was investigated in the OVCAR3 ovarian cancer cell line. Risk association was evaluated in 479 cases of EOC patients and 431 controls. SNPs were analyzed by using polymerase chain reaction based restriction fragment length polymorphism assay. miR-196a expression was evaluated with reverse transcription polymerase chain reaction. The influence of miR-196a-2 rs11614913 T/C on EOC cell migration and invasion ability was further investigated in vitro. The results revealed significant differences in the homozygous CC genotype distribution in patients with EOC (n=479), compared with that of the control subjects (n=431; P=0.026). Analysis of the association between genotype and the risk of EOC revealed that individuals who carried the homozygous CC genotype were 1.34-fold more susceptible to EOC, compared with those carrying the wild-type TT and heterozygous CT genotypes [odds ratio, 1.34; 95% confidence interval, 1.04-2.17; P= 0.023].In addition, the role of this polymorphism in the production of mature miR-196a was investigated. Significantly enhanced production of mature miR-196a was revealed in the C-allelic compared with that of the T-allelic miR-196a-2 precursor (P<0.05). Further examination indicated that miR-196a significantly promoted cell migration and invasion ability in the human OVCAR3 ovarian cell line (P<0.05). In conclusion, the results indicated that the miR-196a-2 rs11614913 CC genotype may increase the risks of ovarian cancer by affecting the expression of mature miR-196a and enhancing cell migration/invasion. The current results provided evidence that the T>C polymorphism in the miR-196a-2 precursor may influence tumorigenesis and metastasis in EOC, and suggested that the functional SNP rs11614913 in the promoter region of pri-miR-196a-2 may be a potential indicator of EOC susceptibility in the population analyzed. IntroductionOvarian cancer only accounts for ~4% of cancer cases in women, but it is the eighth most common cause of cancerassociated mortality resulting from gynecological tumors worldwide (1,2). Epithelial ovarian cancer (EOC), which is categorized into serous, mucinous, endometrioid and non-clear cell types, accounts for 90% of all ovarian cancer (3,4). The earlier cancer ...

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Section: Discussionmentioning

confidence: 99%

Association between the rs11614913 variant of miRNA-196a-2 and the risk of epithelial ovarian cancer

Song

Zhao

et al. 2015

Oncology Letters

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“…The SNP rs895819, located in pre-miR-27a, was evaluated in an association study in which SNPs located in recently identified breast cancer-relevant miRNA genes were examined (including pre-miRNAs and an approximately 200-base pair flanking region) by sequencing of these regions (Slaby et al, 2012). In a group of 1217 German familial breast cancer patients and 1422 unrelated healthy German women, Yang et al (2010) found that the G allele of rs895819, located in the terminal loop of a pre-miR-27a oncogene, was associated with a reduced familial breast cancer risk.…”

Section: Discussionmentioning

confidence: 99%

Associations of miRNA polymorphisms and expression levels with breast cancer risk in the Chinese population

Qi¹,

Wang²,

Zhou³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Single-nucleotide polymorphisms in microRNAs (miRNAs) may dramatically affect gene expression and subsequently alter individual susceptibility to cancer, and thus has become a research hotspot for many cancer types, including breast cancer. We recruited 321 breast cancer patients and 290 controls in our study. Four established miRNA single-nucleotide polymorphisms (mir-499 rs3746444 A>G; miR-27a rs895819 A>G; miR-196a2 rs11614913 T>C; miR-146a rs2910164 G/C) were detected using Taqman assays. Mature miRNA expression, allele distribution, and the association with clinical features were further analyzed. Our results showed that the miR146a rs2910164 G/C polymorphism was associated with an elevated risk of breast cancer (odds ratio = 1.85, 95% confidence interval = 1.03-3.32; P < 0.05). Compared with the ancestral T allele in miR-196a2 rs11614913, the variant C allele was consistently associated with an increased risk of breast cancer (odds ratio = 2.20, 95% confidence interval = 1.19-4.09, P < 0.01) and clinical pathological type (P < 0.01). miR-27a rs895819 A>G and miR-499 rs3746444 A>G were not associated with breast cancer risk. Analysis of mature miRNA expression confirmed that the variant C allele in miR146a rs2910164 and miR-196a2 rs11614913 dramatically inhibited production of their mature products. Our results suggested that miR-146a rs2910164 G>C and miR-196a2 rs11614913 T>C may be biomarkers for predicting breast cancer risk in the Chinese population.

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“…These genes are located within introns or exons of protein-coding genes and in intergenic regions. In addition, miRNAs have been found in many areas of the genome which are associated with cancer development: fragile sites, regions of amplification and LOH regions [11,36,42].…”

Section: Introductionmentioning

confidence: 99%

New miRNA expression abnormalities in laryngeal squamous cell carcinoma

Cybula

Wieteska

Józefowicz-Korczyńska

et al. 2016

CBM

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Abstract. BACKGROUND:Although the development of novel diagnostic and treatment strategies concerning laryngeal cancer is highly intensive, the survival rate remains virtually unchanged. Small non-coding RNAs appear to be very promising biomarkers -and so remain the focus of extensive investigation in laryngeal cancer. OBJECTIVE: We examined the expression of five miRNA and five genes related to cancer whether they could be potential laryngeal cancer biomarkers. METHODS:We performed an analysis in 47 patients diagnosed with laryngeal cancer. The qPCR technique was used to investigate the expression profile. RESULTS: While miR-21-3p and miR-525-5p were found to be significantly up-regulated, miR-139-3p and miR-885-5p expression is lower in laryngeal cancer. Moreover, PIK3R1 and HACE1 were found to be also down-regulated. CONCLUSIONS: The change in miRNA expression is frequent than the expression of other tested genes. The expression of passenger strands such as miR-21-3p and miR-139-3p, which are rarely investigated, is also significantly affected in laryngeal cancer. While PIK3R1, HACE1, miR-139-3p, and miR-885-5p may act as tumor suppressor genes in the studied tumour type, miR-21-3p and miR-525-5p seem to have oncogenic properties. Our findings suggest that miR-885-5p and PIK3R1 are the best indicators for the classification of laryngeal cancer tissue and normal mucosa.

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Genetic polymorphisms and microRNAs: new direction in molecular epidemiology of solid cancer

Cited by 108 publications

References 81 publications

Association between the rs11614913 variant of miRNA-196a-2 and the risk of epithelial ovarian cancer

Association between the rs11614913 variant of miRNA-196a-2 and the risk of epithelial ovarian cancer

Associations of miRNA polymorphisms and expression levels with breast cancer risk in the Chinese population

New miRNA expression abnormalities in laryngeal squamous cell carcinoma

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