Short rare MUC6 minisatellites-5 alleles influence susceptibility to gastric carcinoma by regulating gene

Kwon, Jeong-Ah; Lee, Sangyeop; Ahn, Eun‐Kyung; Seol, So-Young; Kim, Min Chan; Kim, Su Jin; Kim, Kyung Sik; Chu, In-Sun; Leem, Sun‐Hee

doi:10.1002/humu.21289

Cited by 35 publications

(28 citation statements)

References 30 publications

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“…Several previous studies have identified an association between cancer predisposition and minisatellites (Leem et al, 2002;Leem et al, 2004;Jeong et al, 2007;Seol et al, 2008;Yoon et al, 2008;Lee et al, 2009;Kwon et al, 2010). Some minisatellite alleles are associated with human disease and with differential expression of nearby genes (Davidson and Britten, 1979).…”

Section: Discussionmentioning

confidence: 97%

“…The relationship between rare length HRAS minisatellite alleles and cancer risk were implicated by case-control studies (Krontiris et al, 1993;Bennett et al, 1995;Fiskerstrand et al, 1999;MacKenzie and Quinn, 1999). Especially, rare alleles of VNTR are associated with a high risk of various types of cancer (Leem et al, 2002;Leem et al, 2004;Jeong et al, 2007;Seol et al, 2008;Yoon et al, 2008;Lee et al, 2009;Kwon et al, 2010). To ascertain minisatellite influence on gene expression, we examined the effects of flanking luciferase reporter genes with minisatellites.…”

Section: Discussionmentioning

confidence: 99%

“…Allelic variation at VNTRs has been related to the pathogenesis of human genetic diseases, including cancer (Krontiris et al, 1993;Bennett et al, 1995;Fiskerstrand et al, 1999;MacKenzie et al, 1999). Previously, we described an association between variation in minisatellite lengths and cancer predisposition (Leem et al, 2002;Leem et al, 2004;Jeong et al, 2007;Seol et al, 2008;Yoon et al, 2008;Lee et al, 2009;Kwon et al, 2010). In a recent study, we observed that rare alleles of BORIS-MS2 in the younger group (age, < 40 years) were associated with a statistically significant increased risk of breast cancer (Yoon et al, 2010).…”

Section: Introductionmentioning

confidence: 89%

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Variants of BORIS minisatellites and relation to prognosis of prostate cancer

et al. 2011

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BORIS, a member of the cancer-testis antigen family with testis specific expression, showed abnormal expression in various cancer types including prostate cancer. In our previous work, we identified the polymorphic minisatellite, BORIS-MS2, located in the promoter region of BORIS. BORIS-MS2 was revealed as a polymorphic minisatellite that contains seven alleles each with different numbers of the repeat unit. We assessed the association between the allelic variation of BORIS-MS2 and prostate cancer by a case-control study. Using a PCR-based method, 315 cancer-free male controls and 648 cases with prostate cancer were genotyped. There was no significant difference observed in the overall distribution of this minisatellite, which indicates that this polymorphism is not responsible for prostate cancer susceptibility in the Korean population. Additionally, two new rare alleles (9 and 19 copies) were detected in this study, which were identified only in cancer subjects. When we compared the clinicopathological information with the Jewett-Whitmore system of prostate cancer classification, the frequency of rare allele cases in the higher grade was significantly higher than in the total prostate group (P = 0.032). The higher grades in the Jewett-Whitmore system were associated with a poor prognosis. Therefore, this result suggests that the rare alleles of BORIS-MS2 may be used as a marker of poor outcome in prostate cancer patients.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 89%

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Variants of BORIS minisatellites and relation to prognosis of prostate cancer

et al. 2011

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“…Aberrant MUC6 expression was often found in gastrointestinal diseases, in relation to MUC6-MS5 and susceptibility to rectal cancers [116]. MUC6-MS5 sequences with different sizes were found to contain several putative transcription factors binding sites for Hnf4, Maz, E2f1, Pbx, Tal, Bach2 and Krox [115]. Ahn et al [116] suggested that loci of MUC6 MSs may function as a useful predisposition marker of rectal cancer risk particularly to the male gender.…”

Section: Rectal Cancermentioning

confidence: 97%

“…Among these, gastric mucin MUC6 has a role in gastric cancer development [52] and is aberrantly expressed during the progression of some colorectal cancers [114]. MUC6 has five novel tandem repeats (TR) (MUC6-(minisatellite, MS) MS1, -MS2, -MS3, -MS4, -MS5) in intronic regions [115]. Aberrant MUC6 expression was often found in gastrointestinal diseases, in relation to MUC6-MS5 and susceptibility to rectal cancers [116].…”

Section: Rectal Cancermentioning

confidence: 99%

Exploring the role and diversity of mucins in health and disease with special insight into non-communicable diseases

et al. 2015

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Mucins are major glycoprotein components of the mucus that coats the surfaces of cells lining the respiratory, digestive, gastrointestinal and urogenital tracts. They function to protect epithelial cells from infection, dehydration and physical or chemical injury, as well as to aid the passage of materials through a tract i.e., lubrication. They are also implicated in the pathogenesis of benign and malignant diseases of secretory epithelial cells. In Human there are two types of mucins, membrane-bound and secreted that are originated from mucous producing goblet cells localized in the epithelial cell layer or in mucous producing glands and encoded by MUC gene. Mucins belong to a heterogeneous family of high molecular weight proteins composed of a long peptidic chain with a large number of tandem repeats that form the so-called mucin domain. The molecular weight is generally high, ranging between 0.2 and 10 million Dalton and all mucins contain one or more domains which are highly glycosylated. The size and number of repeats vary between mucins and the genetic polymorphism represents number of repeats (VNTR polymorphisms), which means the size of individual mucins can differ substantially between individuals which can be used as markers. In human it is only MUC1 and MUC7 that have mucin domains with less than 40% serine and threonine which in turn could reduce number of PTS domains. Mucins can be considered as powerful two-edged sword, as its normal function protects from unwanted substances and organisms at an arm's length while, malfunction of mucus may be an important factor in human diseases. In this review we have unearthed the current status of different mucin proteins in understanding its role and function in various non-communicable diseases in human with special reference to its organ specific locations. The findings described in this review may be of direct relevance to the major research area in biomedicine with reference to mucin and mucin associated diseases.

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Reduced m6A modification predicts malignant phenotypes and augmented Wnt/PI3K‐Akt signaling in gastric cancer

et al. 2019

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Background As the most abundant epigenetic modification on mRNAs and long non‐coding RNAs, N6‐methyladenosine (m6A) modification extensively exists in mammalian cells. Controlled by writers (methyltransferases), readers (signal transducers), and erasers (demethylases), m6A influences mRNA structure, maturation, and stability, thus negatively regulating protein expression in a post‐translational manner. Nevertheless, current understanding of m6A's roles in tumorigenesis, especially in gastric cancer (GC) remains to be unveiled. In this study, we assessed m6A's clinicopathological relevance to GC and explored the underlying mechanisms. Methods By referring to a proteomics‐based GC cohort we previously generated and the TCGA‐GC cohort, we merged expressions of canonical m6A writers (METTL3/METTL14), readers (YTHDF1/YTHDF2/YTHDF3), and erasers (ALKBH5/FTO), respectively, as W, R, and E signatures to represent m6A modification. We stratified patients according to these signatures to decipher m6A's associations with crucial mutations, prognosis, and clinical indexes. m6A's biological functions in GC were predicted by gene set enrichment analysis (GSEA) and validated by in vitro experiments. Results We discovered that W and R were potential tumor suppressive signatures, while E was a potential oncogenic signature in GC. According to W/R/E stratifications, patients with low m6A‐indications were accompanied with higher mutations of specific genes ( CDH1 , AR , GLI3 , SETBP1 , RHOA , MUC6 , and TP53 ) and also demonstrated adverse clinical outcomes. GSEA suggested that reduced m6A was correlated with oncogenic signaling and phenotypes. Through in vitro experiments, we proved that m6A suppression (represented by METTL14 knockdown) promoted GC cell proliferation and invasiveness through activating Wnt and PI3K‐Akt signaling, while m6A elevation (represented by FTO knockdown) reversed these phenotypical and molecular changes. m6A may also be involved in interferon signaling and immune responses of GC. Conclusions Our work demonstrated that low‐m6A signatures predicted adverse clinicopathological features of GC, while the reduction of RNA m6A methylation activated oncogenic Wnt/PI3K‐Akt signaling and promoted malignant phenotypes of GC cells.

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Short rare MUC6 minisatellites-5 alleles influence susceptibility to gastric carcinoma by regulating gene

Cited by 35 publications

References 30 publications

Variants of BORIS minisatellites and relation to prognosis of prostate cancer

Variants of BORIS minisatellites and relation to prognosis of prostate cancer

Exploring the role and diversity of mucins in health and disease with special insight into non-communicable diseases

Reduced m6A modification predicts malignant phenotypes and augmented Wnt/PI3K‐Akt signaling in gastric cancer

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