The Rare Variant rs35356162 in UHRF1BP1 Increases Bladder Cancer Risk in Han Chinese Population

Wu, Junlong; Wang, Meilin; Chen, Haitao; Xu, Jianfeng; Zhang, Guiming; Gu, Chengyuan; Ding, Qiang; Wei, Qingyi; Zhu, Yao; Ye, Dingwei

doi:10.3389/fonc.2020.00134

Cited by 13 publications

(11 citation statements)

References 38 publications

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“…Moreover, miR-143 restrained the expression of FAM83F and thereby refrained the proliferation, migration, and invasion and induced G1/G0 phase arrest of ESCC cells ( Mao et al, 2016 ). Besides, FAM83F was also found high expression in papillary thyroid cancer ( Fuziwara et al, 2019 ). Furthermore, the functional study had shown that MiR-650 expression in glioma tissues was greatly decreased, while the expression of FAM83F was remarkably up-regulated and MiR-650 could promote cell proliferation through facilitating the expression of FAM83F ( Xu et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…In the past few years, studies have demonstrated abnormal expression in some members of the FAM83 family and their prognostic value. For example, Fuziwara et al (2019) reported that FAM83F , a novel oncogenic protein, was overexpressed in thyroid cancer and cross-regulated MAPK and TGF signaling pathways to promote the biological behavior and differentiation of thyroid follicular cells. FAM83B was recently identified as a novel oncogene involved in activating CRAF/MAPK signaling and driving epithelial cell transformation ( Cipriano et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

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Systematic Analysis of Expression Profiles and Prognostic Significance for FAM83 Family in Non-small-Cell Lung Cancer

Gan

Meng

2020

Front. Mol. Biosci.

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BackgroundLung cancer remains a common malignancy and the leading cause of cancer-related deaths in the world. Although dramatic progress made in multimodal therapies, it still has a poor prognosis. The Family with sequence similarity 83 (FAM83) of poorly characterized proteins are defined by the presence of the conserved DUF1669 domain of unknown function at their N-termini, most of which significantly elevated levels of expression in multiple cancers. However, the expression and prognostic values of different FAM83 family in lung cancer, especially in non-small-cell lung cancer (NSCLC), have not been clarified.MethodsONCOMINE, UALCAN, GEPIA, Kaplan–Meier Plotter, cBioPortal, and STRING databases were utilized in this study.ResultsThe transcriptional levels of FAM83A/B/C/D/F/G/H were up-regulated in patients with NSCLC. A noticeable correlation was found between the over-expressions of FAM83A/B/D/F/H and clinical cancer stages in NSCLC patients. Besides, higher mRNA expressions of FAM83A/B/C/D/F/H were discovered to be expressively associated with overall survival (OS) in lung cancer patients, furthermore, FAM83A, FAM83C, and FAM83H in OS group achieved 0.9475/1, 0.971897/1, and 0.9454545/0.8974359 specificity/sensitivity in distinguishing short survivors from long survivors, respectively. Moreover, a high mutation rate of FAM83 family (51%) was also observed in lung adenocarcinoma (LUAD) patients, and genetic alteration in the FAM83 family was associated with shorter OS and disease-free survival (DFS) in LUAD patients.ConclusionOur results indicated that FAM83A/H might play important roles in NSCLC tumorigenesis and might be risk factor for the survival of NSCLC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Systematic Analysis of Expression Profiles and Prognostic Significance for FAM83 Family in Non-small-Cell Lung Cancer

Gan

Meng

2020

Front. Mol. Biosci.

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“…This can lead to β-catenin accumulation in the cytosol, increased nuclear translocation of activated β-catenin, interactions with members of the T-cell factor (TCF4) transcription factor family, and stimulation of β-catenin-dependent gene expression leading to increased cell proliferation and growth ( 196 ). The role of Wnt/β-catenin signaling in the development of colorectal cancer is now well-recognised ( 197 ) and a functional interaction between estrogen signaling and Wnt/β-catenin pathways has been reported in human colon cancer cells ( 198 ). Recent studies have shown convergence between KCNQ1 and β-catenin regulatory pathways in CRC and the molecular mechanisms regulating KCNQ1:β-catenin interactions and their effects on CRC cell differentiation, proliferation, and invasion ( 199 ).…”

Section: Sexual Dimorphism Of Ion Channel Function In Crcmentioning

confidence: 99%

Sexual Dimorphism in Colon Cancer

et al. 2020

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A higher incidence of colorectal cancer (CRC) is found in males compared to females. Young women (18–44 years) with CRC have a better survival outcome compared to men of the same age or compared to older women (over 50 years), indicating a global incidence of sexual dimorphism in CRC rates and survival. This suggests a protective role for the sex steroid hormone estrogen in CRC development. Key proliferative pathways in CRC tumorigenesis exhibit sexual dimorphism, which confer better survival in females through estrogen regulated genes and cell signaling. Estrogen regulates the activity of a class of Kv channels (KCNQ1:KCNE3), which control fundamental ion transport functions of the colon and epithelial mesenchymal transition through bi-directional interactions with the Wnt/β-catenin signalling pathway. Estrogen also modulates CRC proliferative responses in hypoxia via the novel membrane estrogen receptor GPER and HIF1A and VEGF signaling. Here we critically review recent clinical and molecular insights into sexual dimorphism of CRC biology modulated by the tumor microenvironment, estrogen, Wnt/β-catenin signalling, ion channels, and X-linked genes.

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“…Emerging evidence has revealed that low-frequency variants are associated with prostate [20], lung [18], ovarian [21], and breast cancers [22], but the role of low-frequency variants in the bladder cancer risk remains unclear. Although our previous study described an exome chip analysis and showed that the rare variant rs35356162 in UHRF1BP1 increases the bladder cancer risk [23], the sequencing depth and economic efficiency are inferior to targeted next-generation region sequencing. In addition, targeted sequencing of known risk-associated regions to identify the effects of low-frequency or rare variants on disease has been recognized as a useful approach to help elucidate a further proportion of disease heritability [16,24,25].…”

Section: Introductionmentioning

confidence: 99%

Identification of low-frequency variants of UGT1A3 associated with bladder cancer risk by next-generation sequencing

Zheng

et al. 2021

Oncogene

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Although genome-wide association studies (GWASs) have successfully revealed many common risk variants for bladder cancer, the heritability is still largely unexplained. We hypothesized that low-frequency variants involved in bladder cancer risk could reveal the unexplained heritability. Next-generation sequencing of 113 patients and 118 controls was conducted on 81 genes/ regions of known bladder cancer GWAS loci. A two-stage validation comprising 3,350 cases and 4,005 controls was performed to evaluate the effects of low-frequency variants on bladder cancer risk. Biological experiments and techniques, including electrophoretic mobility shift assays, CRISPR/Cas9, RNA-Seq, and bioinformatics approaches, were performed to assess the potential functions of low-frequency variants. The low-frequency variant rs28898617 was located in the first exon of UGT1A3 and was significantly associated with increased bladder cancer risk (odds ratio = 1.50, P = 3.10 × 10 −6). Intriguingly, rs28898617 was only observed in the Asian population, but monomorphism was observed in the European population. The risk-associated G allele of rs28898617 increased UGT1A3 expression, facilitated UGT1A3 transcriptional activity, and enhanced the binding activity. In addition, UGT1A3 deletion significantly inhibited the proliferation, invasion, and migration of bladder cancer cells and xenograft tumor growth. Mechanistically, UGT1A3 induced LAMC2 expression by binding CBP and promoting histone acetylation, which remarkably promoted the progression of bladder cancer. This is the first targeted sequencing study to reveal that the novel lowfrequency variant rs28898617 and its associated gene UGT1A3 are involved in bladder cancer development, providing new insights into the genetic architecture of bladder cancer.

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The Rare Variant rs35356162 in UHRF1BP1 Increases Bladder Cancer Risk in Han Chinese Population

Cited by 13 publications

References 38 publications

Systematic Analysis of Expression Profiles and Prognostic Significance for FAM83 Family in Non-small-Cell Lung Cancer

Systematic Analysis of Expression Profiles and Prognostic Significance for FAM83 Family in Non-small-Cell Lung Cancer

Sexual Dimorphism in Colon Cancer

Identification of low-frequency variants of UGT1A3 associated with bladder cancer risk by next-generation sequencing

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