On the Protective Effects of Gene SNPs Against Human Cancer

Tan, Hua

doi:10.1016/j.ebiom.2018.06.027

Cited by 14 publications

(8 citation statements)

References 9 publications

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“…This is sensible since not all miRNA-gene pairs sharing regulatory factors exemplify positive correlation due to many complex regulation networks, and cancer cells take advantage of this switch to control miRNA-gene co-expression. For example, a genetic variation in a regulatory region can impact the binding affinity of miRNAs or transcription factors, leading to abnormal gene abundance [61,62]. It should be noted that it is possible that a shared TF may repress both the miRNA and gene in a positive pair, or repress one and simultaneously activate the other.…”

Section: Discussionmentioning

confidence: 99%

Pan-cancer analysis on microRNA-associated gene activation

et al. 2019

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Background While microRNAs (miRNAs) were widely considered to repress target genes at mRNA and/or protein levels, emerging evidence from in vitro experiments has shown that miRNAs can also activate gene expression in particular contexts. However, this counterintuitive observation has rarely been reported or interpreted in in vivo conditions. Methods We systematically explored the positive correlation between miRNA and gene expressions and its potential implications in tumorigenesis, based on 8375 patient samples across 31 major human cancers from The Cancer Genome Atlas (TCGA). Findings We found that positive miRNA-gene correlations are surprisingly prevalent and consistent across cancer types, and show distinct patterns than negative correlations. The top-ranked positive correlations are significantly involved in the immune cell differentiation and cell membrane signaling related processes, and display strong power in stratifying patients in terms of survival rate. Although intragenic miRNAs generally tend to co-express with their host genes, a substantial portion of miRNAs shows no obvious correlation with their host gene plausibly due to non-conservation. A miRNA can upregulate a gene by inhibiting its upstream suppressor, or shares transcription factors with that gene, both leading to positive correlation. The miRNA/gene sites associated with the top-ranked positive correlations are more likely to form super-enhancers compared to randomly chosen pairs. Wet-lab experiments revealed that positive correlations partially remain in in vitro condition. Interpretation Our study brings new insights into the critical role of miRNA in gene regulation and the complex mechanisms underlying miRNA functions, and reveals both biological and clinical significance of miRNA-associated gene activation.

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Section: Discussionmentioning

confidence: 99%

Pan-cancer analysis on microRNA-associated gene activation

et al. 2019

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“…We also conducted the expression quantitative trait loci (eQTL) analysis using GTEx portal website (http://www.gtexp ortal.org/ home/), to predict the influence of SNPs on expression level of LIN28A. 10 Statistical significance was defined when P < .05. The SAS release 9.1 (SAS Institute) was adopted to conduct all statistical analyses.…”

Section: Discussionmentioning

confidence: 99%

“…A probability of <.2 was considered a noteworthy association. We also conducted the expression quantitative trait loci (eQTL) analysis using GTEx portal website (http://www.gtexportal.org/home/), to predict the influence of SNPs on expression level of LIN28A . Statistical significance was defined when P < .05.…”

Section: Methodsmentioning

confidence: 99%

LIN28A gene polymorphisms confer Wilms tumour susceptibility: A four‐centre case‐control study

Zhang

Liu

et al. 2019

J Cellular Molecular Medi

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Wilms tumour is a renal malignancy that commonly occurs in children. LIN28A gene overexpression has been reported to be involved in various human malignancies, while its roles in Wilms tumour risk are still under investigation. Here, we genotyped four LIN28A polymorphisms in 355 Wilms tumour patients and 1070 healthy controls from four hospitals in China. The genotyped single nucleotide polymorphisms (SNPs) include the following: rs3811464 G>A, rs3811463 T>C, rs34787247 G>A and rs11247957 G>A. Overall, we found that rs3811463 T>C and rs34787247 G>A were associated with increased risk of Wilms tumour. Combination analysis of risk genotypes showed that, compared to non‐carriers, subjects with 1 risk genotype and 1‐3 risk genotypes were more likely to develop Wilms tumour, with an adjusted odds ratio (OR) of 1.58 and 1.56, respectively. Stratified analysis further demonstrated that the risk effect remained prominent in some subgroups. We also found that presence of 1‐3 risk genotypes was associated with Wilms tumour risk in subgroups > 18 months of age, females, males and those with clinical stage I + II diseases. Furthermore, expression quantitative trait locus (eQTL) analysis indicated that rs3811463 C allele was significantly associated with increased transcripts of LIN28A gene. These findings suggest that LIN28A gene polymorphisms may be associated with increased predisposition to Wilms tumour.

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“…Although most of the research performed to date focus on disease‐causing genetic variants and on genetic profiles related to a guarded prognosis, the recognition of the full spectrum of susceptibility genotypes offers a broader understanding of the complex pathways that drive to the neoplastic transformation. In fact, several recent reports emphasize the importance of cancer‐preventive genetic variants in guiding the clinical decision process and as a valuable therapeutic target …”

Section: Discussionmentioning

confidence: 99%

Influence of E‐cadherin genetic variation in canine mammary tumour risk, clinicopathological features and prognosis

Canadas

Santos

Medeiros

et al. 2019

Vet Comparative Oncology

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E-cadherin is a cell adhesion molecule that participates in several cellular processes that guarantee the maintenance of structural and functional integrity of epithelial tissues. E-cadherin plays an important role in mammary carcinogenesis, and various studies have demonstrated the effect of CDH1 genetic variation in risk, progression and biological behaviour of human breast cancer. Although there are some recognized genetic variations in canine CDH1 gene, their influence in canine mammary tumour development and progression has not been previously evaluated. In this study, we aim to assess the influence of CDH1 SNPs rs850805755, rs852280880 and rs852639930 in the risk, clinicopathological features and clinical outcome of canine mammary tumours. A case-control study was conducted involving 206 bitches with mammary tumours and 161 bitches free of mammary neoplasia. CDH1 SNPs rs850805755 and rs852280880 were associated with a decreased risk and a later onset of mammary tumour development. Furthermore, these SNPs were related to the development of small size carcinomas, of low histological grade and low nuclear pleomorphism. SNP rs852639930 was associated with the development of small size tumours with a non-infiltrative, noninvasive growth pattern. Data from the present investigation demonstrate that these CDH1 genetic variants could have a protective role in canine mammary tumours, by being associated with low risk of tumour development, delayed onset of the disease and less aggressive clinicopathological features. K E Y W O R D S canine mammary tumour, CDH1 gene, E-cadherin, risk, SNP

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On the Protective Effects of Gene SNPs Against Human Cancer

Cited by 14 publications

References 9 publications

Pan-cancer analysis on microRNA-associated gene activation

Pan-cancer analysis on microRNA-associated gene activation

LIN28A gene polymorphisms confer Wilms tumour susceptibility: A four‐centre case‐control study

Influence of E‐cadherin genetic variation in canine mammary tumour risk, clinicopathological features and prognosis

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