MicroRNA Genetic Variation: From Population Analysis to Functional Implications of Three Allele Variants Associated with Cancer

Torruella‐Loran, Ignasi; Laayouni, Hafid; Dobon, Begoña; Gallego, Alicia; Balcells, Ingrid; García-Ramallo, Eva; Espinosa‐Parrilla, Yolanda

doi:10.1002/humu.23045

Cited by 16 publications

(26 citation statements)

References 70 publications

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“…We found that most of the SNPs (1833 SNPs, 97.5%, Table S1 ) in miRNA seed regions were rare variants (defined as SNPs with minor allele frequency (MAF) < 5%). Recently, Torruella-Loran et al [ 18 ] studied miRNA genetic variation in human populations and found that the seed regions tend to be depleted of high-frequency variants, which is consistent with our finding. We also found that there are 1587, 749, 340, 102, 31, and 4 miRNAs, which carry zero, one, two, three, four, and five SNPs, respectively, in their seed region (Figure S1 , Table S1 ).…”

Section: Resultssupporting

confidence: 92%

Clustering Pattern and Functional Effect of SNPs in Human miRNA Seed Regions

Zhao

et al. 2018

International Journal of Genomics

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miRNAs are a class of noncoding RNAs important in posttranscriptional repressors and involved in the regulation of almost every biological process by base paring with target genes through sequence in their seed regions. Genetic variations in the seed regions have vital effects on gene expression, phenotypic variation, and disease susceptibility in humans. The distribution pattern of genetic variation in miRNA seed regions might be related to miRNA function and is worth paying more attention to. We here employed computational analyses to explore the clustering pattern and functional effect of SNPs in human miRNA seed regions. A total of 1879 SNPs were mapped to 1226 human miRNA seed regions. We found that miRNAs with SNPs in their seed region are significantly enriched in miRNA clusters. We also found that SNPs in clustered miRNA seed regions have a lower functional effect than have SNPs in nonclustered miRNA seed regions. Additionally, we found that clustered miRNAs with SNPs in seed regions are involved in more pathways. Overall, our results demonstrate that SNPs in clustered miRNA seed regions can take part in more intricate and complex gene-regulating networks with lower functional cost by functional complementarity. Moreover, our results also broaden current knowledge on the genetic variation in human miRNA seed regions.

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Section: Resultssupporting

confidence: 92%

Clustering Pattern and Functional Effect of SNPs in Human miRNA Seed Regions

Zhao

et al. 2018

International Journal of Genomics

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“…Our result was consistent with the Thakur et al results [42]. In 2016, Torruella-Loran et al found that rs11614913 in miR-196a2 has a function in regulating the expression of several genes involved in cancer [43]. SNPs located in the mature sequences of miRNA genes might affect miRNA biogenesis and recognition of target mRNAs [16].…”

Section: Discussionsupporting

confidence: 91%

Polymorphisms in miRNA genes play roles in the initiation and development of cervical cancer

Zhang¹,

Zhou²,

Li³

et al. 2019

J. Cancer

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MicroRNA deregulation is crucial for cancer development. Studies showed that polymorphisms in miRNA genes could affect miRNA expression, which might be associated with cancer development. In the current study, we investigated the association of seven single nucleotide polymorphisms (SNPs) in seven miRNA genes with the initiation and development of cervical cancer in a Chinese Han population. The SNPs of 358 cervical intraepithelial neoplasia (CIN) patients, 547 cervical cancer patients and 567 healthy individuals were genotyped using TaqMan assays. Moreover, we evaluated the association of the seven SNPs with the different stages of cervical cancer. Our results showed that rs4636297 in miR-126 was associated with susceptibility to CIN and cervical cancer (P=0.019 and 0.019, respectively) and that the T allele was associated with a higher risk of CIN (OR=1.334, 95% CI: 1.049-1.698) and cervical cancer (OR=1.296, 95% CI: 1.044-1.609). Similarly, rs11614913 in miR-125a was associated with CIN and cervical cancer (P=0.025 and 0.015, respectively), and the T allele might be the protective factor for CIN (OR=0.807, 95% CI: 0.669-0.974) and cervical cancer (OR=0.814, 95% CI: 0.689-0.961). Our results indicated that rs4636297 in miR-126 and rs11614913 in miR-196a2 play an important role only in the initiation of cervical cancer not in the development of CIN to cervical cancer.

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“…In fact, it has been demonstrated previously that the variant GG genotype of the polymorphism had the lowest delta CT value (which implied a high expression level), followed by AG and AA genotypes, although it was not clear whether the difference was statistically significant 26 . It has also been reported in an in vitro study that miR-499a originating from the two alleles of rs3746444 polymorphism reduced the expression of tumor suppressor genes to different extents 35 . Considering these previous findings, we postulate that the variant allele of the polymorphism gave rise to a higher level of miR-499a and caused a significant decrease in the expression of tumor suppressor genes, thereby leading to an increase in breast cancer susceptibility.…”

Section: Discussionmentioning

confidence: 85%

Association between MIR499A rs3746444 polymorphism and breast cancer susceptibility: a meta-analysis

Tan

Lim

Fang

et al. 2020

Sci Rep

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Numerous studies have investigated the association of MIR499A rs3746444 polymorphism with breast cancer susceptibility, but the results have been inconsistent. In this work, we performed a meta-analysis to obtain a more reliable estimate of the association between the polymorphism and susceptibility to breast cancer. A comprehensive literature search was conducted on PubMed, Scopus, Web of Science (WoS), China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases up to January 2020. A total of 14 studies involving 6,797 cases and 8,534 controls were included for analysis under five genetic models: homozygous (GG vs. AA), heterozygous (AG vs. AA), dominant (AG + GG vs. AA), recessive (GG vs. AA + AG) and allele (G vs. A). A statistically significant association was observed between the polymorphism and an increased breast cancer susceptibility under all genetic models (homozygous, OR = 1.33, 95% CI = 1.03-1.71, P = 0.03; heterozygous, OR = 1.08, 95% ci = 1.00-1.16, P = 0.04; dominant, OR = 1.15, 95% CI = 1.02-1.30; P = 0.03; recessive, OR = 1.35, 95% ci = 1.06-1.72, P = 0.01; allele, OR = 1.12, 95% CI = 1.00-1.26, P = 0.04). Subgroup analysis based on ethnicity suggested that significant association was present only among Asians, but not Caucasians. In conclusion, MIR499A rs3746444 polymorphism was significantly associated with breast cancer susceptibility among Asians, suggesting its potential use as a genetic risk marker in this population.

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MicroRNA Genetic Variation: From Population Analysis to Functional Implications of Three Allele Variants Associated with Cancer

Cited by 16 publications

References 70 publications

Clustering Pattern and Functional Effect of SNPs in Human miRNA Seed Regions

Clustering Pattern and Functional Effect of SNPs in Human miRNA Seed Regions

Polymorphisms in miRNA genes play roles in the initiation and development of cervical cancer

Association between MIR499A rs3746444 polymorphism and breast cancer susceptibility: a meta-analysis

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