A Polymorphism at the microRNA Binding Site in the 3′ Untranslated Region of <i>KRT81</i> Is Associated with Breast Cancer

Sha, Ziyue; Lai, Ruixue; Zhang, Xiaoyun; Zhao, Yufei; Wu, Jianhua; Chen, Geng; Guo, Zhanjun

doi:10.1089/dna.2019.5179

Cited by 8 publications

(5 citation statements)

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“…SNPs in the miRNA binding sites can alter miRNA-mRNA binding affinity, which alters expression of the corresponding genes, thereby affecting cell proliferation, apoptosis and development. This process is associated with susceptibility to diseases, including cancer and autoimmune diseases (20,28,29). Here, SNP rs16917496 in the miR-502 binding site of the 3'-UTR of SET8 mRNA was associated with the occurrence of RA; low SET8 and higher ROS levels and decreased IL-10 expression were associated with CC genotype and increased risk of RA.…”

Section: Discussionmentioning

confidence: 91%

“…Keratin 81 (KRT81) is a member of the keratin gene family that encodes hair keratin, which is a key component of the intermediate filaments and maintains mechanical stability and integrity of epithelial cells (19). Moreover, SNP rs3660 in the miRNA binding site of the 3'-UTR of KRT81 mediates the expression of KRT81 (20,21). In previous studies, miR-SNPs have been associated with the risk of RA (11,12); therefore, the present case-control study aimed to assess the association of miR-SNPs with risk of RA.…”

Section: Introductionmentioning

confidence: 99%

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Polymorphisms in microRNA binding site of SET8 regulate the risk of rheumatoid arthritis

et al. 2023

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Rheumatoid arthritis (RA) is a complex, heterogeneous, progressive and long-term autoimmune disease characterized by symmetrical joint inflammation and bone erosion. The etiology of RA is unclear, but its pathogenesis is associated with oxidative stress and inflammatory cytokines. Single nucleotide polymorphisms (SNPs) in the microRNA (miRNA)-binding sites modify the development of rheumatic disease by regulating the expression of target genes. The present study investigated whether SNPs in the miRNA binding site in the 3' untranslated region (3'-UTR) of SET domain containing lysine methyltransferase) 8 (SET8) and Keratin 81 (KRT81), namely rs16917496 and rs3660, respectively, were associated with the occurrence of RA. The polymerase chain reaction-ligase detection reaction assay showed that the distribution frequencies of the CC genotype (P=0.025) of SNP rs16917496 in SET8 were significantly higher in patients with RA than in healthy controls, which indicated that the CC genotype was associated with an increased risk of RA. SET8 expression in the blood samples of CC genotype carriers was lower than that of TT genotype carriers. Moreover, the CC genotype carriers exhibited higher reactive oxygen species (ROS) levels (1011.500±536.426 vs. 548.616±190.508, P=0.032) and lower interleukin-10 (IL-10) levels (P<0.001). The present study demonstrated that SNP rs16917496 in the 3'-UTR of SET8 was a predictor of RA risk and may regulate RA development by mediating expression of SET8, thereby regulating the levels of ROS and IL-10.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Polymorphisms in microRNA binding site of SET8 regulate the risk of rheumatoid arthritis

et al. 2023

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“…Cells were cultured for 72 h in an incubator, and the supernatant was used for IL-8 measurement using LEGENDplex Multi-analyte flow assay kit (Biolegend, San Diego, CA) according to manufacturer’s instructions as we have previously described. 30 …”

Section: Methodsmentioning

confidence: 99%

Dicer Suppresses Hepatocellular Carcinoma via Interleukin-8 Pathway

Han

Sha

et al. 2023

Clin Med Insights Oncol

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Background: Elevated level of interleukin-8 (IL-8) promotes hepatocellular carcinoma (HCC) development and contributes to poor prognosis. Previously, we have proved that Dicer inhibits HCC progression. In this study, we evaluated the potential interaction between IL-8 and Dicer as well as their influence on HCC. Methods: Hepatocellular carcinoma cells of SMMC-7721 were divided into 2 groups for subsequent analysis: pCMV-Dicer group for Dicer-overexpressing lentivirus transfected cells (pCMV-Dicer cells) and pCMV-NC group for empty lentivirus transfected cells (pCMV-NC cells). Cell Counting kit-8 (CCK8), wound healing, and transwell were used to evaluate the inhibitory effect of Dicer overexpression on proliferation, migration, and invasion of HCC cells. The level of IL-8 was measured by flow cytometry bead-based immunoassays. Male nude BALB/c mice injected with pCMV-Dicer or pCMV-NC cell suspensions was used for transplant of HCC tumor. Results: We found that the secretion of IL-8 was reduced in the medium of pCMV-Dicer cells ( P = .027). Recombinant human IL-8 (rhIL-8) reversed the inhibitory effect of Dicer on proliferation ( P < .01), migration ( P = .003), and invasion ( P = .001), whereas IL-8 inhibitor of reparixin enhanced inhibitory effect of Dicer on proliferation ( P < .05), migration ( P = .008), and invasion ( P = .000). Lenvatinib downregulated the IL-8 level of HCC cells ( P = .000) as well as promote Dicer-induced inhibition for HCC cells referring to proliferation ( P < .05), migration ( P = .000), and invasion ( P = .000). Animal experiments also demonstrated that Dicer cooperated with lenvatinib to inhibit the growth of HCC tumors ( P < .05). Conclusions: Dicer cooperated with lenvatinib to inhibit HCC growth via downregulating IL-8, and Dicer displayed its potential capability to enhance the anti-tumor effect of lenvatinib.

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“…There is now ample evidence in a range of different diseases including pre-eclampsia (Li et al, 2021), type 2 diabetes (Yan et al, 2021), lung fibrosis after lung transplantation (Wang et al, 2020), non-alcoholic fatty liver disease (López-Sánchez et al, 2021), liver cancer (Ghafouri-Fard et al, 2021) and multiple sclerosis (Shareef et al, 2021), that polymorphisms in the relevant miRNA can confer susceptibility and determine the effectiveness of suppression of gene expression. In addition, polymorphisms in the miRNA binding domain of target gene regions play a role in diseases such as colorectal cancer where SNPs in the solute carrier transporter gene predict clinical outcome in colorectal cancer (Bendova et al, 2020) and the KRT81 gene in breast cancer (Sha et al, 2020). There are numerous other examples in this everexpanding field of research (Liu et al, 2021;Vohra et al, 2020).…”

Section: Micro-rna Moleculesmentioning

confidence: 99%

The importance of establishing genetic phase in clinical medicine

Tait

2021

Int J Immunogenetics

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Haplotyping or determination of genetic phase has always played a pivotal role in MHC (HLA studies) both in helping to understand inheritance patterns in diseases such as type 1 diabetes (T1D) and in ensuring better matching in transplantation scenarios such as haematopoietic stem cell transplantation (HSCT), using donors genetically related to the patient. In recent years the need to establish genetic phase in a number of clinical scenarios has become apparent. These include:1. Genetic phasing for hematopoietic stem cell transplants using unrelated donors, where the HLA haplotypes are not known but where haplotype-matched recipients fare better clinically than allele matched, but haplotype mismatched patients.2. The use of checkpoint inhibitors is one of the most innovative and exciting developments in cancer treatment in years. An example is the use of the monoclonal ipilimumab to block the CTLA-4 receptor which is known to contain polymorphic sites.Until the phase of these polymorphisms is known it will not be possible to determine how effectively this monoclonal will perform in individual patients.3. The role of miRNA single strand molecules and their effect on gene expression. Thousands of non-coding genes have been identified and have been shown to be polymorphic, as have their target genes. Genetic phasing of polymorphism both in the miRNA source genes and their targets is clearly a fertile area of research 4. In areas such a drug metabolism where the polymorphic family of CYP genes is responsible for the metabolism of the majority of prescription drugs, determining phase of SNPs is critical to understanding drug metabolism and efficacy. 5. In multigenic disease studies combinations of single nucleotide polymorphisms (SNPs) in participating genes require accurate phasing in order to fully appreciate their role in the disease process. In addition, the level of expression of genes (point 3) is also important in understanding disease processes at the functional level. This review outlines the techniques that are currently available for approximating phase and discusses the clinical relevance of establishing genetic phase in areas of clinical medicine outlined in points 1-3.

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A Polymorphism at the microRNA Binding Site in the 3′ Untranslated Region of KRT81 Is Associated with Breast Cancer

Cited by 8 publications

References 40 publications

Polymorphisms in microRNA binding site of SET8 regulate the risk of rheumatoid arthritis

Polymorphisms in microRNA binding site of SET8 regulate the risk of rheumatoid arthritis

Dicer Suppresses Hepatocellular Carcinoma via Interleukin-8 Pathway

The importance of establishing genetic phase in clinical medicine

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