The has-miR-526b Binding-Site rs8506G&gt;A Polymorphism in the lincRNA-NR_024015 Exon Identified by GWASs Predispose to Non-Cardia Gastric Cancer Risk

Fan, Qingxia; Yu, Rong; Huang, Wei-Xian; Cui, Xueying; Luo, Bing-Hui; Zhang, Liyuan

doi:10.1371/journal.pone.0090008

Cited by 30 publications

(20 citation statements)

References 39 publications

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“…Luciferase report assay showed that the rs6976789 variant T allele influenced the binding ability of miR-148a. Similar research have been done in GC [33,34,35]. …”

Section: Discussionsupporting

confidence: 59%

Genetic Variations and Gastric Cancer

Yu¹,

Chen²

2015

Gastrointest Tumors

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Background: Gastric cancer (GC) has an apparent hereditary component. However, in a large fraction of gastric cases, no known genetic syndrome or family history can be identified, suggesting the presence of ‘missing heritability' in GC etiology. Genome-wide association studies (GWAS) and traditional candidate gene studies have both led to the identification of multiple replicable common genetic variants associated with GC risk. Summary: We summarize the genetic variants associated with GC risk identified up to date. Achievements derived from translational cancer research including the following aspects: (a) contribution to the our understanding of gastric tumorigenesis, (b) guidance to individualized treatment and (c) prediction of patient prognosis. We also prospect future research direction such as post-GWAS analyses and rare variants studies. Key Message: Many genetic variants were found through GWAS or candidate gene studies, and interpreting their underlying mechanisms will help us translate risk profiles generated from these variations into use in the clinical setting for targeted screening and treatment. Practical Implications: Investigation of the potential use of genetic variations as prognostic and predictive markers is a developing field. Many people could benefit from a better understanding of genetic polymorphisms to potentially identify a priori individuals who might have the best chance of survival and therefore derive most clinical benefit from treatment. Outcomes of particular scientific interest for molecular epidemiologic studies should include overall survival, recurrence- and progression-free survival, response to treatment, and early and late toxicities stemming from chemotherapy and radiation.

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“…Luciferase report assay showed that the rs6976789 variant T allele influenced the binding ability of miR-148a. Similar research have been done in GC [33,34,35]. …”

Section: Discussionsupporting

confidence: 59%

Genetic Variations and Gastric Cancer

Yu¹,

Chen²

2015

Gastrointest Tumors

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“…Until now, investigation into the role of hsa-miR-526b has been very limited. A recent genome-wide association study found that the hsa-miR-526b binding-site rs8506G > A polymorphism in the lincRNA-NR_024015 exon predisposes Chinese people to a higher risk of non-cardiac gastric cancer [32]. Hsa-miR-526b is identified as one of the pregnancy-associated miRNAs found in maternal plasma [33].…”

Section: Discussionmentioning

confidence: 99%

By downregulating Ku80, hsa-miR-526b suppresses non-small cell lung cancer

Zhang

et al. 2014

Oncotarget

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Ku80 is involved in DNA double-strand breaks (DSBs) repair. Ku80 is overexpressed in lung cancer tissues, yet, molecular mechanisms have not been examined. We identified that miRNA, hsa-miR-526b, is bound to the 3′-UTR of Ku80 mRNA, thus decreasing Ku80 expression in NSCLC cells. Hsa-miR-526b was downregulated in NSCLC tissues compared with corresponding non-tumorous tissues, and its expression was inversely correlated with Ku80 upregulation. Overexpression of Ku80 and downregulation of hsa-miR-526b were associated with poor clinical outcomes of NSCLC patients. Hsa-miR-526b suppressed NSCLC cell proliferation, clonogenicity, and induced cell cycle arrest and apoptosis. Hsa-miR-526b inhibited xenografts and orthotopic lung tumor growth. Further, Ku80 knockdown in NSCLC cells suppressed tumor properties in vitro and in vivo similar to hsa-miR-526b overexpression. In agreement, Ku80 restoration partially reversed cell cycle arrest and apoptosis induced by hsa-miR-526b in NSCLC cells in vitro and in vivo. In addition, hsa-miR-526b overexpression or Ku80 knockdown increased p53 and p21CIP1/WAF1 expression. These findings reveal that hsa-miR-526b is a potential target in cancer therapy.

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“…The rs13252298 and rs1456315 were associated with significantly decreased risks of CRC. Similarly, rs217727 AA in H19 and rs8506G > A in lincRNA‐NR_024015 are associated with increased risk of bladder cancer and non‐cardia gastric cancer, respectively.…”

Section: Lncrna Snps In Cancer Risk Predictionmentioning

confidence: 97%

Potential of long non‐coding RNAs in cancer patients: From biomarkers to therapeutic targets

Gupta

Tripathi

2016

Intl Journal of Cancer

432

260

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Because of high specificity and easy detection in the tissues, serum, plasma, urine and saliva, interest in exploring the potential of long non-coding RNAs (lncRNAs) in cancer patients continues to increase. LncRNAs have shown potential as a biomarker in the diagnosis and prognosis of bladder cancer, prostate cancer, gastric cancer, pancreatic cancer, breast cancer and many other cancer types. Some lncRNAs have also been used as adjunct to improve the specificity and sensitivity of existing biomarkers. The molecular tools such as RNA-seq, RNA-FISH, ic-SHAPE and quantitative real-time PCR have been used for examining the lncRNAs' potential. Some lncRNAs such as PCA3 is now routinely used in the clinic for the diagnosis of prostate cancer. Single nucleotide polymorphisms (SNPs) in lncRNAs can also be used as a predictor of cancer risk. Although ongoing studies continue to unravel the underlying mechanism, some lncRNAs have been used as therapeutic targets for the selective killing of cancer cells in patients. Thus lncRNAs are emerging as convenient and minimally invasive diagnostic/prognostic markers, and also as therapeutic target. Companies such as the Curna Inc., MiNA Therapeutics Ltd. and RaNA Therapeutics Inc. have been taking steps to develop lncRNA based strategies against cancer. In this review, we discuss the potential of lncRNAs as biomarkers and therapeutic targets in cancer patients.

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The has-miR-526b Binding-Site rs8506G>A Polymorphism in the lincRNA-NR_024015 Exon Identified by GWASs Predispose to Non-Cardia Gastric Cancer Risk

Cited by 30 publications

References 39 publications

Genetic Variations and Gastric Cancer

Genetic Variations and Gastric Cancer

By downregulating Ku80, hsa-miR-526b suppresses non-small cell lung cancer

Potential of long non‐coding RNAs in cancer patients: From biomarkers to therapeutic targets

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