Dephosphorylation of the Retinoblastoma protein (Rb) inhibits cancer cell EMT via Zeb

Egger, Jacklynn V.; Lane, Maria; Antonucci, Lisa; Dedi, Brixhilda; Krucher, Nancy A.

doi:10.1080/15384047.2016.1235668

Cited by 31 publications

(21 citation statements)

References 46 publications

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“…Zinc finger E-box-binding protein (ZEB) serves an important role in cell differentiation and embryonic development (7). It has been reported that ZEB is associated with biological processes, including tumor invasion and metastasis (8). Although embryo implantation into the endometrium is similar to the invasion mechanism of tumors, limited research has been conducted on ZEB in pernicious PP (9).…”

Section: Introductionmentioning

confidence: 99%

The role of Zeb1 in the pathogenesis of morbidly adherent placenta

Yang

et al. 2019

Mol Med Report

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Zinc finger E-box-binding homeobox 1 (Zeb1) is a promoter of epithelial-mesenchymal transformation, which may serve an important role in morbidly adherent placenta (MAP). In the present study, the protein expression levels of Zeb1 were examined in the placenta tissues of 60 patients, including 20 patients with placenta accreta (PA) and 20 patients with placenta previa without PA (UPA) and 20 patients in late pregnancy that delivered by cesarean section (normal). The expression levels of Zeb1, N-cadherin, vascular endothelial growth factor (VEGF), Tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2), and tumor necrosis factor-related apoptosis-inducing ligand-receptor 3 (TRAIL-R3) were higher in PA tissues compared with in normal control tissues. The expression levels of E-cadherin and TRAIL-R2 were decreased in PA tissues compared with in normal control tissues. These findings indicated that Zeb1 may serve an important role in placental attachment, thus promoting the development of dangerous PA. Overexpression of Zeb1 may upregulate the expression levels of N-cadherin, VEGF, TRAIL-R3, cyclin D1 and Bcl-2, and downregulate the expression levels of E-cadherin and TRAIL-R2. In addition, Zeb1 regulated the viability, apoptosis and migration of HTR-8/SV neo cells and human umbilical vein endothelial cells by regulating the Akt pathway. In conclusion, these findings indicated that Zeb1 may promote placental implantation by activating the Akt signaling pathway, thus providing a theoretical basis for investigating the causes of MAP.

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Section: Introductionmentioning

confidence: 99%

The role of Zeb1 in the pathogenesis of morbidly adherent placenta

Yang

et al. 2019

Mol Med Report

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“… 38 Dephosphorylation of the Rb, which leads to the activation of Rb, inhibits cancer cell EMT via Zeb. 39 The Rb also plays a pivotal role in the negative control of the cell cycle and in tumor progression. 40 Regarding the key role of p53-p21-Rb signaling in cell proliferation and mobility, we finally found that RNF126 promoted cell proliferation, drug resistance, and cell mobility in vitro via inhibiting p53/p21 in ubiquitin-dependent degradation.…”

Section: Discussionmentioning

confidence: 99%

<p>Overexpression of RNF126 Promotes the Development of Colorectal Cancer via Enhancing p53 Ubiquitination and Degradation</p>

Wang¹,

Wang²,

Wang³

et al. 2020

OTT

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Background RING finger protein 126 (RNF126), as a novel E3 ubiquitin ligase, plays an oncogenic role in several solid cancers. But its potential role in colorectal cancer (CRC) that harbored 50% mutant p53, to our knowledge, is rarely reported. Materials and Methods We investigated the clinical significance and relationship of RNF126 and p53 in CRC tissues and cells. Meanwhile, WB, qRT-PCR, co-IP, MTT, and transwell were used to investigate the function and molecular mechanism of RNF126 in regulating malignant biology in vitro. Results RNF126 was overexpressed in human CRC specimens, which was tightly associated with tumor size ( P =0.021), T stage ( P =0.030), lymph node metastasis ( P =0.006), TNM stage ( P =0.001), and the poor survival ( P =0.003) of CRC patients. RNF126 had no association with p53 mutation in CRC specimens, and in p53 mutant Colo-205 and SW620 cells. However, in p53 wildtype HCT116 and HCT-8 cells, RNF126 silencing upregulated p53 and p21 but inhibited Rb phosphorylation at Serine 780 (pRb), which was inhibited by p53siRNA. Conversely, RNF126 overexpression downregulated p53 and p21 but promoted pRb expression, which was reversed by a classic proteasome inhibitor, MG132. However, the mRNA levels of above target genes were unchanged, implying a ubiquitination dependent post-translational modification involving in above regulation. Meanwhile, RNF126 was co-immunoprecipitated with p53 and p21 to form a triple complex. RNF126 silencing and overexpression inhibited and promoted p53 ubiquitination and degradation in vitro, respectively. In addition, p53siRNA reversed RNF126 silencing-inhibited cell proliferation, drug resistance, and cell mobility in HCT116 cells. Conversely, MG132 inhibited RNF126 overexpression-promoted above cell biology in HCT-8 cells. Conclusion Overexpression of RNF126 was remarkably associated with multiple advanced clinical characters of CRC patients independent of mutant p53. RNF126 promotes cell proliferation, mobility, and drug resistance in CRC via enhancing p53 ubiquitination and degradation.

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“…24 In recent years, related studies have revealed that EMT is indispensable for tumor cell growth and survival. 25 In this study, we investigated the effects of carboplatin on the cytotoxicity of Rb cells through the lncRNA XIST/miR-200a-3p/NRP1 axis and found that carboplatin and micro-RNA-34a could inhibit EMT of Rb cells. The proliferation, invasion and ETM inhibition of Rb cells in carboplatin combined with siRNA-LncRNA XIST intervention group were stronger than those in carboplatin or siRNA-LncRNA XIST intervention group alone.…”

Section: Discussionmentioning

confidence: 99%

<p>Carboplatin Inhibits the Progression of Retinoblastoma Through IncRNA XIST/miR-200a-3p/NRP1 Axis</p>

Zhao¹,

Wan²,

Zhu³

2020

DDDT

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Objective: This study was set out to explore the expression and related mechanism of XIST and miR-200a-3p in retinoblastoma (Rb). Patients and Methods: Fifty-four children with Rb who came to our hospital for surgery from January 2018 to September 2019 were collected. In addition, Rb cells and human retinal epithelial cells were purchased. XIST-siRNA (si-XIST), XIST-shRNA (sh-XIST), empty vector plasmid (siRNA-NC), miR-200a-3p-mimics and miR −200a-3p-inhibition were transfected into Y79 cells. The expression of XIST and miR-200a-3p in the samples were determined by qRT-PCR. β-catenin, cyclin B1, cyclin D1, Bax, Caspase-3, N-cadherin, vimentin, Snail, E-Cadherin and ZO-1 protein levels were measured by WB. MTT, Transwell and flow cytometry were utilized to detect cell proliferation, invasion, and apoptosis, respectively. Results: XIST was highly expressed while miR-200a-3p was lowly expressed in patients' tissues, and the AUC of both was over 0.8. XIST and miR-200a-3p was related to differentiation degree in Rb patients. Y79 cells were selected for transfection. Compared with the siRNA-NC group, XIST was significantly reduced in the siRNA-XIST group, and it was significantly increased in the shRNA-XIST group (P<0.01). The proliferation capacity of siRNA-XIST group was decreased, while that of shRNA-XIST group was up-regulated. The apoptosis rate of siRNA-XIST group was significantly up-regulated, while that of shRNA-XIST group was decreased (P<0.001). The invasive capacity of siRNA-XIST group was decreased, while that of shRNA-XIST group was up-regulated (P<0.001). Silencing XIST and over-expressed miR-200a-3p could inhibit cell epithelial-mesenchymal transition (EMT), proliferation, invasion, and promote apoptosis. WB detection showed that Carboplatin + LncRNA XIST intervention group could more significantly inhibit β-catenin, cyclin B1, cyclin D1, N-cadherin, vimentin, Snail protein, and promote the up-regulation of Bax, Caspase-3, E-Cadherin and ZO-1 expression. Conclusion: Inhibition of XIST expression can up-regulate miR-200a-3p-mediated PI3K-Akt/MAPK-ERK signaling pathway and affect cell EMT, proliferation, invasion, and apoptosis, which is expected to be a potential therapeutic target for Rb.

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Dephosphorylation of the Retinoblastoma protein (Rb) inhibits cancer cell EMT via Zeb

Cited by 31 publications

References 46 publications

The role of Zeb1 in the pathogenesis of morbidly adherent placenta

The role of Zeb1 in the pathogenesis of morbidly adherent placenta

<p>Overexpression of RNF126 Promotes the Development of Colorectal Cancer via Enhancing p53 Ubiquitination and Degradation</p>

<p>Carboplatin Inhibits the Progression of Retinoblastoma Through IncRNA XIST/miR-200a-3p/NRP1 Axis</p>

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