WTIP interacts with BRCA2 and is essential for BRCA2 centrosome localization in cervical cancer cell

Zhang, Jun; Xu, Jing; Wang, Guoqing; Park, Sun; Yan, Tao; Zhao, Xiaoling

doi:10.1007/s00404-016-4176-9

Cited by 5 publications

(4 citation statements)

References 31 publications

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“…Modulation of WTIP can lead to the kidney-cell scarring (e.g., focal segmental glomerulosclerosis) that is characteristic in diabetes mellitus 40,41 . Thus, alterations to WTIP may be associated with obesity associated comorbidities, including diabetes 42 .…”

Section: Resultsmentioning

confidence: 99%

Comprehensive and Systematic Analysis of Gene Expression Patterns Associated with Body Mass Index

Joseph

Jaime-Lara

Wang³

et al. 2019

Sci Rep

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Both genetic and environmental factors are suggested to influence overweight and obesity risks. Although individual loci and genes have been frequently shown to be associated with body mass index (BMI), the overall interaction of these genes and their role in BMI remains underexplored. Data were collected in 90 healthy, predominately Caucasian participants (51% female) with a mean age of 26.00 ± 9.02 years. Whole blood samples were assayed by Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. We integrated and analyzed the clinical and microarray gene expression data from those individuals to understand various systematic gene expression patterns underlying BMI. Conventional differential expression analysis identified seven genes RBM20, SEPT 12, AX748233, SLC30A3, WTIP, CASP10 , and OR12D3 associated with BMI. Weight gene co-expression network analysis among 4,647 expressed genes identified two gene modules associated with BMI. These two modules, with different extents of gene connectivity, are enriched for catabolic and muscle system processes respectively, and tend to be regulated by zinc finger transcription factors. A total of 246 hub genes were converted to non-hub genes, and 286 non-hub genes were converted to hub genes between normal and overweight individuals, revealing the network dynamics underlying BMI. A total of 28 three-way gene interactions were identified, suggesting the existence of high-order gene expression patterns underlying BMI. Our study demonstrated a variety of systematic gene expression patterns associated with BMI and thus provided novel understanding regarding the genetic factors for overweight and obesity risks on system levels.

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Section: Resultsmentioning

confidence: 99%

Comprehensive and Systematic Analysis of Gene Expression Patterns Associated with Body Mass Index

Joseph

Jaime-Lara

Wang³

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Wt1-interacting protein (WTIP), an Ajuba family LIM domain scaffold protein expressed in podocytes, coordinates cell adhesion changes and transcriptional responses to regulate podocyte phenotypic plasticity 28. Downregulation of WTIP abolished BRCA2 centrosome localization and abnormal cell division in HeLa cells 29. It has been reported that WTIP can work as a crucial point of crosstalk between EGFR and Hippo signaling and suppress the Hippo pathway 30.…”

Section: Discussionmentioning

confidence: 99%

CBX2 Regulates Proliferation and Apoptosis via the Phosphorylation of YAP in Hepatocellular Carcinoma

et al. 2019

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Chromobox 2 (CBX2), a chromobox family protein, is a crucial component of the polycomb group complex: polycomb repressive complex 1 (PRC1). Research on CBX2 as an oncogene has been published in recent years. However, the connection between CBX2 and hepatocellular carcinoma (HCC) has not been studied. In this article, based on the results of immunohistochemical (IHC) staining of HCC and adjacent liver tissue microarrays, we found that high CBX2 expression is associated with poor prognosis in HCC patients. The results of a CCK8 assay, a clonogenic survival assay and a nude mouse tumorigenicity assay showed that knockdown of CBX2 inhibited the proliferation of HCC cells. According to the results of Annexin V-FITC/propidium iodide (PI) staining-based fluorescence activated cell sorting (FACS) analysis, knockdown of CBX2 increased HCC cell apoptosis. Furthermore, the RNA-seq results revealed that knockdown of CBX2 inhibited the expression of WTIP, which is an inhibitor of the Hippo pathway. We used western blotting to validate the mechanism and discovered that knockdown of CBX2 increased the phosphorylation of YAP, which explains why knockdown of CBX2 inhibits proliferation and increases apoptosis in HCC cells. In conclusion, CBX2 could be a potential target for HCC anticancer treatment.

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“…Previous studies suggested that WTIP is a candidate tumor suppressor. In cervical cancer cells, downregulation of WTIP abolished BRCA2mediated centrosome localization and resulted in abnormal cell division, suggesting that WTIP might be involved in the development of cervical cancer [19]. A recent study reported that WTIP is downregulated in NSCLC, and low levels of WTIP are associated with poor prognosis in NSCLC patients [20].…”

Section: Discussionmentioning

confidence: 99%

“…As a member of mammalian P-body associated protein, WTIP is involved in miRNA-mediated gene silencing in human osteosarcoma cells [18]. In cervical cancer cells, downregulation of WTIP abolished BRCA2-mediated centrosome localization and resulted in abnormal cell division, suggesting that WTIP might be involved in the development of cervical cancer [19]. Recently, it was demonstrated that WTIP protein expression is significantly reduced in non-small-cell lung cancer (NSCLC) cells, and WTIP downregulation is associated with poor prognosis in NSCLC patients [20].…”

Section: Introductionmentioning

confidence: 99%

WTIP upregulates FOXO3a and induces apoptosis through PUMA in acute myeloid leukemia

et al. 2021

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Acute myeloid leukemia (AML) is an aggressive and heterogeneous clonal hematologic malignancy for which novel therapeutic targets and strategies are required. Emerging evidence suggests that WTIP is a candidate tumor suppressor. However, the molecular mechanisms of WTIP in leukemogenesis have not been explored. Here, we report that WTIP expression is significantly reduced both in AML cell lines and clinical specimens compared with normal controls, and low levels of WTIP correlate with decreased overall survival in AML patients. Overexpression of WTIP inhibits cell proliferation and induces apoptosis both in vitro and in vivo. Mechanistic studies reveal that the apoptotic function of WTIP is mediated by upregulation and nuclear translocation of FOXO3a, a member of Forkhead box O (FOXO) transcription factors involved in tumor suppression. We further demonstrate that WTIP interacts with FOXO3a and transcriptionally activates FOXO3a. Upon transcriptional activation of FOXO3a, its downstream target PUMA is increased, leading to activation of the intrinsic apoptotic pathway. Collectively, our results suggest that WTIP is a tumor suppressor and a potential target for therapeutic intervention in AML.

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WTIP interacts with BRCA2 and is essential for BRCA2 centrosome localization in cervical cancer cell

Abstract: This study indicates that WTIP interacts with BRCA2 and might be responsible for BRCA2 centrosome localization in cervical cancer cell.

Cited by 5 publications

References 31 publications

Comprehensive and Systematic Analysis of Gene Expression Patterns Associated with Body Mass Index

Comprehensive and Systematic Analysis of Gene Expression Patterns Associated with Body Mass Index

CBX2 Regulates Proliferation and Apoptosis via the Phosphorylation of YAP in Hepatocellular Carcinoma

WTIP upregulates FOXO3a and induces apoptosis through PUMA in acute myeloid leukemia

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