Genetic alterations of WWOX in Wilms’ tumor are involved in its carcinogenesis

Płuciennik, Elżbieta; Nowakowska, Magdalena; Wujcicka, Wioletta; Sitkiewicz, Anna; Kazanowska, Bernarda; Zielińska, Małgorzata

doi:10.3892/or.2012.1940

Cited by 27 publications

(32 citation statements)

References 29 publications

(37 reference statements)

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“…The WWOX gene has been identified as a candidate susceptible gene for many diseases by previous studies, in which several SNPs were reported to be associated with risk of multiple diseases, including lung cancer, gastric cancer, hypertension, wilms's tumor, breast cancer, thyroid carcinoma, ovarian cancer, myeloma and so on . In current study, we were the first to find evidence the WWOX gene deletion (CNV‐67048) was associated with increased risk of gliomas.…”

Section: Discussionmentioning

confidence: 56%

Association study of a functional copy number variation in the WWOX gene with risk of gliomas among Chinese people

Fan

Ding

et al. 2014

Intl Journal of Cancer

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Gliomas represents more than 80% of all malignant brain tumors. However, the etiology still remains largely unknown. Human WW domain-containing oxidoreductase (WWOX), which is located at 16q23.1-16q23.2, the common fragile site 16D (FRA16D), an area with a high frequency of gene deletions or chromosomal alterations, has been identified as a tumor suppressor gene in multiple cancers. In current study, we analyzed the WWOX deletion (CNV-67048) in a large, case-control study of 3,622 adult Chinese people (including 1,798 glioma cases and 1,824 healthy controls). All participants were genotyped using realtime qualitative PCR (qPCR), and its biological effect was validated with mRNA expression assays. The deletion was significantly associated with glioma risk, with ORs (95% CIs) of 1.21 (1.05-1.41) associated with 1 copy deletion and 1.94 (1.37-2.75) associated with 2 copy deletion as compared with subjects with no deletion (p for trend 5 8.05 3 10 26 ). Additional adjustments and stratified analyses did not change the results materially. The mRNA levels of WWOX in glioma tissues were significantly lower than that of their border tissues (p 5 0.007), especially in the loss genotyped subjects. Our data suggest that the loss genotypes of CNV-67048 in WWOX gene predispose their carriers to gliomas, and WWOX gene deletion may be a new biomarker for predicting risk of gliomas.

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Section: Discussionmentioning

confidence: 56%

Association study of a functional copy number variation in the WWOX gene with risk of gliomas among Chinese people

Fan

Ding

et al. 2014

Intl Journal of Cancer

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“…It has been confirmed to be altered in various types of cancer including breast, lung, gastric, ovarian, Wilms' tumor and glioblastoma multiforme (7)(8)(9)(10)(11)(12)(13). Genetic and epigenetic alterations of this gene include loss of heterozygosity (LOH) and promoter methylation.…”

Section: Introductionmentioning

confidence: 99%

The WWOX tumor suppressor gene in endometrial adenocarcinoma

Płuciennik

Kośla

Wójcik‐Krowiranda

et al. 2013

International Journal of Molecular Medicine

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Abstract. Endometrial cancer is a lethal malignancy, the causes of which remain to be determined. The aim of the present study, carried out on tumor samples from 79 patients, was to evaluate the role of the WWOX tumor suppressor gene in endometrial adenocarcinoma. The expression levels of WWOX and its protein content were assessed in normal endometrium and cancer samples. Quantitative PCR was used to assess the correlation between the expression levels of WWOX and the genes involved in the proliferation (MKI67), apoptosis (BAX, BCL2), signal transduction (EGFR), cell cycle (CCNE1, CCND1), cell adhesion (CDH1) and transcription regulation (TP73, NCOR1). The relationship between loss of hetero zygosity (LOH) and WWOX mRNA levels was also investigated using high resolution melting. Results of the present study demonstrated a positive correlation of WWOX expression with BCL2 and CCND1 and a negative correlation with BAX, CDH1, NCOR1 and BCL2/BAX ratio. The results also showed that loss of heterozygosity at two analyzed loci of the WWOX gene is frequent in patients with endometrial cancer and that WWOX expression levels are lower in tumor samples than in normal tissue. In conclusion, WWOX may be involved in endometrial cancer.

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“…Recently, many molecules have been reported to be involved in the development and metastasis of prostate cancer including cyclin D1, retinoblastoma, p53 and WW domain-containing oxidoreductase (WWOX). 5 Several of these molecules tightly regulate the cell cycle, indicating that disorder of the cell cycle is an important event in prostate cancer pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

WWOX suppresses prostate cancer cell progression through cyclin D1-mediated cell cycle arrest in the G1 phase

Lin

Chang

et al. 2015

Cell Cycle

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(2015) WWOX suppresses prostate cancer cell progression through cyclin D1-mediated cell cycle arrest in the G1 phase, Cell Cycle, 14:3, 408-416, DOI: 10.4161/15384101.2014 WW domain-containing oxidoreductase (WWOX) has been reported to be a tumor suppressor in multiple cancers, including prostate cancer. WWOX can induce apoptotic responses to inhibit tumor progression, and the other mechanisms of WWOX in tumor suppression have also been reported recently. In this study, we found significant down-regulation of WWOX in prostate cancer specimens and prostate cancer cell lines compared with the normal controls. In addition, an ectopically increased WWOX expression repressed tumor progression both in vitro and in vivo. Interestingly, overexpression of WWOX in 22Rv1 cells led to cell cycle arrest in the G1 phase but did not affect sub-G1 in flow cytometry. GFP-WWOX overexpressed 22Rv1 cells were shown to inhibit cell cycle progression into mitosis under nocodazole treatment in flow cytometry, immunoblotting and GFP fluorescence. Further, cyclin D1 but not apoptosis correlated genes were down-regulated by WWOX both in vitro and in vivo. Restoration of cyclin D1 in the WWOXoverexpressed 22Rv1 cells could abolish the WWOX-mediated tumor repression. In addition, WWOX impair c-Junmediated cyclin D1 promoter activity. These results suggest that WWOX inhibits prostate cancer progression through negatively regulating cyclin D1 in cell cycle lead to G1 arrest. In summary, our data reveal a novel mechanism of WWOX in tumor suppression.

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Genetic alterations of WWOX in Wilms’ tumor are involved in its carcinogenesis

Cited by 27 publications

References 29 publications

Association study of a functional copy number variation in the WWOX gene with risk of gliomas among Chinese people

Association study of a functional copy number variation in the WWOX gene with risk of gliomas among Chinese people

The WWOX tumor suppressor gene in endometrial adenocarcinoma

WWOX suppresses prostate cancer cell progression through cyclin D1-mediated cell cycle arrest in the G1 phase

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