Extensive sequence variation in the 3′ untranslated region of the<i>KRAS</i>gene in lung and ovarian cancer cases

Kim, Minlee; Chen, Xiaowei; Chin, Lena J.; Paranjape, Trupti; Speed, William C.; Kídd, Kenneth K.; Zhao, Hongyu; Weidhaas, Joanne B.; Slack, Frank J.

doi:10.4161/cc.27941

Cited by 35 publications

(28 citation statements)

References 64 publications

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“…The mutation in the KRAS proto-oncogene is frequently detected in several cancers including HCC (Park et al, 2013a,b;Hou et al, 2014;Jung et al, 2014;Zou et al, 2014). Recently, a genetic variant of rs712 in the 3'untranslated region of the KRAS gene has been reported to be functional in the regulation of KRAS by disrupting the complementary site of let-7 and miR-181 (Kumar et al, 2007;Wang et al, 2012;Kim et al, 2014). The rs712 G allele altered the secondary structure of KRAS and resulted in 15% derepression in luciferase expression compared to that in the wild-type in HeLa cells (Kim et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

An let-7 KRAS rs712 polymorphism increases hepatocellular carcinoma risk

Xiong¹,

Song²,

Xiong³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. KRAS, also known as V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog, acts as an intracellular signal transducer. The oncogenic KRAS mutation is an essential step in the development of many types of human cancers, including hepatocellular carcinoma. Here we aimed to investigate the relationship between KRAS rs712 polymorphisms and hepatocellular carcinoma susceptibility. Five-hundred-and-fourteen participants were enrolled in a case-control study (262 cases and 252 normal subjects). The variants were distinguished using polymerase chain reaction-restriction fragment length polymorphism. Significantly increased HCC risk was observed to be associated with the T allele of the rs712 locus (P = 0.049, OR = 1.35, 95%CI = 1.01 -1.78). Further, HCC risk with the GT genotype (P = 0.015, OR = 1.64, 95%CI = 1.08-2.50) and the TT genotype (P = 0.015, OR = 2.56, 95%CI = 1.05-6.25) in a codominant model was significantly higher than that with the GG genotype. In a dominant model, significantly increased HCC susceptibility was also associated with T allele carriers (P = 0.006, OR = 1.75, 95%CI = 1.16-2.63). Moreover, we found that the frequency of the KRAS rs712 TT genotype was significantly higher in HBV-positive HCC patients than in HBV-negative HCC patients.

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Section: Introductionmentioning

confidence: 99%

An let-7 KRAS rs712 polymorphism increases hepatocellular carcinoma risk

Xiong¹,

Song²,

Xiong³

et al. 2015

Genet. Mol. Res.

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“…MicroRNAs (miRNAs) are endogenous non-coding single-stranded RNAs of about 21-22 nucleotides in length, which can regulate gene translation and modulate gene expression at post-transcriptional level during the most biological and pathological processes (Lagos-Quintana et al, 2001). At present, many researchers (Saunders et al, 2007) considered that single nucleotide polymorphisms (SNPs) in the miRNA seed sequence have higher probability of affecting miRNAs function.…”

Section: Inferring Single Nucleotide Polymorphisms In Microrna Bindinmentioning

confidence: 99%

“…Many studies evaluated the possible associations between lung cancer and polymorphisms (Chen et al, 2013;Cheng et al, 2013;Zu et al, 2013;Kim et al, 2014). In this study, we selected lung cancer-related genes that belong to inflammation pathways responding to microorganism and cigarette smoking and hoped to catalogue SNPs, which might affect the expression levels of the target genes.…”

Section: Inferring Single Nucleotide Polymorphisms In Microrna Bindinmentioning

confidence: 99%

Inferring Single Nucleotide Polymorphisms in MicroRNA Binding Sites of Lung Cancer-related Inflammatory Genes

He¹,

Zheng²,

Luo³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Single nucleotide polymorphisms located at microRNA (miRNA)-binding sites are likely to affect the expression of miRNA targets and may contribute to the susceptibility of humans to common diseases. Here 335 candidate lung cancer-related inflammatory genes were selected according to the existing literature and database. We identified putative miRNA-binding sites of 149 genes by specialised algorithms and screened SNPs in the 3'UTRs of these genes. By calculating binding free energy, we sorted 269 SNPs on the basis of the possibility of prediction. The proposed approach could help to easy the identification of functionally relevant SNPs and minimize the workflow and the costs.

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“…The protein product of the normal KRAS gene performs an essential function in normal tissue signaling, and regulates a variety of biological processes, including cellular proliferation and apoptosis 16. The mutation of KRAS gene is an essential step in the development of many cancers 17, particularly the mutation in the coding region of the KRAS gene, one of the major oncogenic mutation found in human cancer, which result in hyper-activation of the protein 18.…”

Section: Introductionmentioning

confidence: 99%

Association between the KRAS Gene Polymorphisms and Papillary Thyroid Carcinoma in a Chinese Han Population

Ning

Rao

et al. 2016

J. Cancer

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Several studies have reported the association between MAPK signaling pathway gene polymorphisms and papillary thyroid carcinoma (PTC). KRAS gene, an oncogene from the mammalian RAS gene family plays an important role in the MAPK pathway. This study aimed to identify the potential association of KRAS gene polymorphisms with susceptibility to PTC in a Han Chinese population.A total of 861 patients with PTC, 562 disease controls with nodular goiter and 897 healthy controls were recruited. Four tagSNP polymorphisms (rs12427141, rs712, rs7315339 and rs7960917) of KRAS gene were genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Statistical analyses and haplotype estimations were conducted using Haploview and Unphased softwares.Only significant differences were observed in genotypic frequencies of the rs7315339 polymorphism (χ2 =7.234, df=2, p=0.027) between PTC and disease controls. Statistically significant differences in both allelic and genotypic genotypes frequencies for rs712 (Genotype, χ2=8.258, p=0.016) and rs12427141 (Allele, χ2=3.992, p=0.046; Genotype, χ2=8.140, p=0.017) were observed between PTC patients and controls. Haplotype analyses revealed higher frequencies of GA and TA haplotypes (p=0.039 and p=0.003, respectively) from rs712- rs12427141 (two-SNP) or TGA and TTG haplotype containing the alleles from rs7960917, rs712 and rs12427141, as well as the GAT haplotype containing the alleles from rs712, rs12427141 and rs7315339 in PTC patients than in healthy controls (p=0.042, p=0.037, p=0.027, respectively). Inversely, the haplotype TTA from rs7960917, rs712 and rs12427141 or the haplotype TAC from rs712, rs12427141 and rs7315339 was significantly less frequent in the PTC patients than in normal control (p=0.003, p=0.003, respectively).These findings suggest the role of these KRAS gene variants in susceptibility to PTC. Moreover, significant differences of the KRAS gene polymorphisms may occur between nodular goiter and PTC.

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Extensive sequence variation in the 3′ untranslated region of theKRASgene in lung and ovarian cancer cases

Cited by 35 publications

References 64 publications

An let-7 KRAS rs712 polymorphism increases hepatocellular carcinoma risk

An let-7 KRAS rs712 polymorphism increases hepatocellular carcinoma risk

Inferring Single Nucleotide Polymorphisms in MicroRNA Binding Sites of Lung Cancer-related Inflammatory Genes

Association between the KRAS Gene Polymorphisms and Papillary Thyroid Carcinoma in a Chinese Han Population

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