The set gene is a potential oncogene in human colorectal adenocarcinoma and oral squamous cell carcinoma

Jiang, Qin; Zhu, Jianjun; Chen, Qianming; Chen, Yao

doi:10.3892/mmr.2011.526

Cited by 6 publications

(8 citation statements)

References 20 publications

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“…I2PP2A (SET) and CIP2A, the endogenous inhibitors of PP2A, have been shown to be overexpressed in numerous cancer types [27] , [31] including chronic myelogenous leukemia [32] , cholangiocarcinoma [33] , colorectal and squamous cell cancer [34] , and neuroblastoma [35] . Amplification of the MYCN oncogene is the most important negative prognostic indicator in neuroblastoma [36] .…”

Section: Discussionmentioning

confidence: 99%

Investigation of PP2A and Its Endogenous Inhibitors in Neuroblastoma Cell Survival and Tumor Growth

Williams

Garner

Waters

et al. 2019

Translational Oncology

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High-risk neuroblastoma continues to carry a poor prognosis. Nearly 50% of these tumors relapse following extensive treatment regimens. Protein phosphatase 2A (PP2A), a tumor suppressor, has been shown to be downregulated in many human cancers via multiple mechanisms including upregulation of its endogenous inhibitors, I2PP2A or CIP2A. We hypothesized that inhibition of the endogenous PP2A inhibitors or activation of PP2A would decrease tumorigenicity in human neuroblastoma cells. Four human neuroblastoma cell lines were utilized. Expression of PP2A and its endogenous inhibitors I2PP2A and CIP2A was confirmed by immunoblotting. PP2A activation was measured via phosphatase activation assay. Multiple parallel methods including siRNA inhibition of the endogenous PP2A inhibitors and pharmacologic activation of PP2A were utilized. Cell viability, proliferation, migration, and invasion assays were performed. In vivo studies were utilized to determine the effects of PP2A activation on neuroblastoma tumor growth. Inhibition of the endogenous inhibitors of PP2A or pharmacologic activation of PP2A with the PP2A activator FTY720 led to decreased neuroblastoma cell viability, proliferation, migration, and invasion. Treatment of mice bearing SK-N-AS or SK-N-BE(2) neuroblastoma tumors with FTY720 resulted in a significant decrease in tumor growth compared to vehicle-treated animals. In conclusion, activation of PP2A may provide a novel therapeutic target for neuroblastoma.

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Section: Discussionmentioning

confidence: 99%

Investigation of PP2A and Its Endogenous Inhibitors in Neuroblastoma Cell Survival and Tumor Growth

Williams

Garner

Waters

et al. 2019

Translational Oncology

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“…Previously, it has been demonstrated that SET upregulation, which leads to PP2A inhibition, is critical for BCR/ABL-positive cells to fulfill their tumorigenic potential (14). Recently, Jiang et al (6) reported that SET was overexpressed at the mRNA level in 21 tumor samples (70.0%) compared with the corresponding normal tissues. The results of the present study also identified that SET expression (at the mRNA level) in 31 patients was markedly increased in 70.9% of tumor specimens compared with adjacent normal tissues.…”

Section: Discussionmentioning

confidence: 99%

“…SET is critical for colorectal adenocarcinoma cell growth, since SET knockdown by specific siRNA results in significantly promoting apoptosis in vivo (6). Previously, Koldobskiy et al (28) showed that p53 is a tumor suppressor of which numerous mutations have been found in >50% of malignancies.…”

Section: Discussionmentioning

confidence: 99%

“…It is predicted to encode a 27-amino acid protein with a molecular weight of 39 kDa. SET is overexpressed and has been found to play a role in acute myeloid leukemia oral carcinoma and ovarian cancer (6–9), but its involvement in the development of colorectal adenocarcinoma remains unknown. In order to determine whether SET is involved in the carcinogenesis of colorectal adenocarcinoma and the Wnt signaling pathway, the mRNA expression of SET , protein phosphatase 2 ( PP2A) and β- catenin in human colorectal adenocarcinoma and paratumor normal tissues was determined by quantitative real-time polymerase chain reaction (qPCR) analysis.…”

Section: Introductionmentioning

confidence: 99%

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Involvement of SET in the Wnt signaling pathway and the development of human colorectal cancer

Zhu

Wen

et al. 2014

Oncology Letters

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The SET oncoprotein is involved in cancer progression by modulating multiple cellular processes, including the inhibition of the tumor suppressor, protein phosphatase 2 (PP2A). Based upon these multiple activities, we hypothesized that targeted inhibition of SET is likely to have multiple discrete and measurable effects on cancer cells. In the present study, the mRNA expression levels of SET, PP2A and β-catenin were examined in 31 pairs of human colorectal adenocarcinoma tissues and corresponding adjacent normal colorectal tissues by quantitative real-time polymerase chain reaction (qPCR). A small interfering RNA targeting SET was transfected into the human colon carcinoma cell lines, LS174T and SW480. The mRNA levels of SET, PP2A, β-catenin, c-Myc, E-cadherin and p53 were determined by qPCR analysis and the protein levels of SET, c-Myc, PP2A and β-catenin were examined by western blot analysis. mRNA expression levels of SET and β-catenin were found to be elevated in 22 (70.9%) samples, while PP2A expression levels were upregulated in eight (25.8%) samples. In addition, the knockdown of SET mRNA expression caused the upregulation of PP2A and c-Myc in the two cell lines, whereas β-catenin, E-cadherin and p53 mRNA expression was downregulated. Consistent with these results, the protein expression of β-catenin and c-Myc was found to be downregulated, whereas PP2A was upregulated at the protein level. Based on these results, we proposed that SET is essential in the carcinogenesis of human colorectal adenocarcinoma. In addition, it is suggested that SET promotes carcinogenesis through regulation of the Wnt signaling pathway.

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“…SET is a multifunctional oncoprotein, involved in apoptosis, transcription, nucleosome assembly and histone binding, which ultimately promotes the initiation and progression of cancer. 4 The SET protein has two isoforms, which were named as isoform 1 and isoform 2, and both were potent inhibitors of protein phosphatase 2A (PP2A). 5 Overexpression of SET was characterized as being tumor-specific and was associated with the worse clinical outcomes in many human malignant carcinomas.…”

Section: Introductionmentioning

confidence: 99%

<p>Upregulated SET Promotes Cell Survival Through Activating Akt/NF-κB Signal in Colorectal Carcinoma</p>

Zhu¹,

Shi²,

Du³

et al. 2020

CMAR

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Purpose: SET has been proven to be an oncogene, which promotes the initiation and progression in several kinds of malignant carcinomas. However, the expression and its functional roles in colorectal carcinoma (CRC) remained unknown. Materials and Methods: CRC tissues samples, CRC cell lines and xenograft mouse tumors were used in this study. The mRNA and protein expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), and Western blot (WB), respectively. siRNAs were used to silence the gene expression. Cell viability, cell proliferation, colony formation, and apoptosis were measured by MTS assay, EdU incorporation assay, plated colony formation assay, and flow cytometry, respectively. Western blot was applied to evaluate the levels of Akt, p-Akt, c-Myc and cyclin D1. Xenograft mouse model was performed to observe the role of SET in vivo. Results: Our results revealed that SET was up-regulated in CRC, and the expression of SET was increased with the development of CRC. SET knockdown in vitro attenuated cell proliferation activity, and increased cell apoptosis in CRC cells. Moreover, the knockdown of SET reduces tumorigenic potential in nude mice. For the mechanism, knockdown of SET promoted the dephosphorylation of Akt, followed by suppressing the translocation of NF-κB to nucleus. In addition, SET knockdown-mediated dephosphorylation of Akt downregulated the expression of c-Myc and Cyclin D1, which inhibited the cell survival in CRC. Conclusion: Our results indicated that SET promoted cell survival via activating Akt/NF-κB signaling pathway in CRC, which strongly suggested that SET might be a potential therapeutic target in the colorectal carcinoma treatment.

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The set gene is a potential oncogene in human colorectal adenocarcinoma and oral squamous cell carcinoma

Cited by 6 publications

References 20 publications

Investigation of PP2A and Its Endogenous Inhibitors in Neuroblastoma Cell Survival and Tumor Growth

Investigation of PP2A and Its Endogenous Inhibitors in Neuroblastoma Cell Survival and Tumor Growth

Involvement of SET in the Wnt signaling pathway and the development of human colorectal cancer

<p>Upregulated SET Promotes Cell Survival Through Activating Akt/NF-κB Signal in Colorectal Carcinoma</p>

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