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N-myc downstream-regulated gene 1 inhibits the proliferation of colorectal cancer through emulative antagonizing NEDD4-mediated ubiquitylation of p21

N-myc downstream-regulated gene 1 (NDRG1) has been shown to play a key role in tumor metastasis. Recent studies demonstrate that NDRG1 can suppress tumor growth and is related to tumor proliferation; however, the mechanisms underlying these effects remain obscure. Immunohistochemistry (IHC) was used... Full description

Journal Title: Journal of Experimental & Clinical Cancer Research 01 December 2019, Vol.38(1), pp.1-15
Main Author: Sen Zhang
Other Authors: Chaoran Yu , Xiao Yang , Hiju Hong , Jiaoyang Lu , Wenjun Hu , Xiaohui Hao , Shuchun Li , Batuer Aikemu , Guang Yang , Zirui He , Luyang Zhang , Pei Xue , Zhenghao Cai , Junjun Ma , Lu Zang , Bo Feng , Fei Yuan , Jing Sun , Minhua Zheng
Format: Electronic Article Electronic Article
Language: English
Subjects:
P21
ID: E-ISSN: 1756-9966 ; DOI: 10.1186/s13046-019-1476-5
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title: N-myc downstream-regulated gene 1 inhibits the proliferation of colorectal cancer through emulative antagonizing NEDD4-mediated ubiquitylation of p21
format: Article
creator:
  • Sen Zhang
  • Chaoran Yu
  • Xiao Yang
  • Hiju Hong
  • Jiaoyang Lu
  • Wenjun Hu
  • Xiaohui Hao
  • Shuchun Li
  • Batuer Aikemu
  • Guang Yang
  • Zirui He
  • Luyang Zhang
  • Pei Xue
  • Zhenghao Cai
  • Junjun Ma
  • Lu Zang
  • Bo Feng
  • Fei Yuan
  • Jing Sun
  • Minhua Zheng
subjects:
  • Ndrg1
  • Tumor Proliferation
  • P21
  • Ubiquitylation
  • Nedd4
  • Medicine
ispartof: Journal of Experimental & Clinical Cancer Research, 01 December 2019, Vol.38(1), pp.1-15
description: N-myc downstream-regulated gene 1 (NDRG1) has been shown to play a key role in tumor metastasis. Recent studies demonstrate that NDRG1 can suppress tumor growth and is related to tumor proliferation; however, the mechanisms underlying these effects remain obscure. Immunohistochemistry (IHC) was used to detect NDRG1 and p21 protein expression in colorectal cancer tissue, and clinical significance of NDRG1 was also analyzed. CCK-8 assay, colony formation assay, flow cytometry, and xenograft model were used to assess the effect of NDRG1 on tumor proliferation in vivo and in vitro. The mechanisms underlying the effect of NDRG1 were investigated using western blotting, immunofluorescence, immunoprecipitation, and ubiquitylation assay. NDRG1 was down-regulated in CRC tissues and correlated with tumor size and patient survival. NDRG1 inhibited tumor proliferation through increasing p21 expression via suppressing p21 ubiquitylation. NDRG1 and p21 had a positive correlation both in vivo and in vitro. Mechanistically, E3 ligase NEDD4 could directly interact with and target p21 for degradation. Moreover, NDRG1 could emulatively antagonize NEDD4-mediated ubiquitylation of p21, increasing p21 expression and inhibit tumor proliferation. Our study could fulfill potential mechanisms of the NDRG1 during tumorigenesis and metastasis, which may serve as a tumor suppressor and potential target for new therapies in human colorectal cancer.
language: eng
source:
identifier: E-ISSN: 1756-9966 ; DOI: 10.1186/s13046-019-1476-5
fulltext: fulltext_linktorsrc
issn:
  • 1756-9966
  • 17569966
url: Link


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titleN-myc downstream-regulated gene 1 inhibits the proliferation of colorectal cancer through emulative antagonizing NEDD4-mediated ubiquitylation of p21
creatorSen Zhang ; Chaoran Yu ; Xiao Yang ; Hiju Hong ; Jiaoyang Lu ; Wenjun Hu ; Xiaohui Hao ; Shuchun Li ; Batuer Aikemu ; Guang Yang ; Zirui He ; Luyang Zhang ; Pei Xue ; Zhenghao Cai ; Junjun Ma ; Lu Zang ; Bo Feng ; Fei Yuan ; Jing Sun ; Minhua Zheng
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subjectNdrg1 ; Tumor Proliferation ; P21 ; Ubiquitylation ; Nedd4 ; Medicine
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descriptionN-myc downstream-regulated gene 1 (NDRG1) has been shown to play a key role in tumor metastasis. Recent studies demonstrate that NDRG1 can suppress tumor growth and is related to tumor proliferation; however, the mechanisms underlying these effects remain obscure. Immunohistochemistry (IHC) was used to detect NDRG1 and p21 protein expression in colorectal cancer tissue, and clinical significance of NDRG1 was also analyzed. CCK-8 assay, colony formation assay, flow cytometry, and xenograft model were used to assess the effect of NDRG1 on tumor proliferation in vivo and in vitro. The mechanisms underlying the effect of NDRG1 were investigated using western blotting, immunofluorescence, immunoprecipitation, and ubiquitylation assay. NDRG1 was down-regulated in CRC tissues and correlated with tumor size and patient survival. NDRG1 inhibited tumor proliferation through increasing p21 expression via suppressing p21 ubiquitylation. NDRG1 and p21 had a positive correlation both in vivo and in vitro. Mechanistically, E3 ligase NEDD4 could directly interact with and target p21 for degradation. Moreover, NDRG1 could emulatively antagonize NEDD4-mediated ubiquitylation of p21, increasing p21 expression and inhibit tumor proliferation. Our study could fulfill potential mechanisms of the NDRG1 during tumorigenesis and metastasis, which may serve as a tumor suppressor and potential target for new therapies in human colorectal cancer.
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titleN-myc downstream-regulated gene 1 inhibits the proliferation of colorectal cancer through emulative antagonizing NEDD4-mediated ubiquitylation of p21
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Abstract Background N-myc downstream-regulated gene 1 (NDRG1) has been shown to play a key role in tumor metastasis. Recent studies demonstrate that NDRG1 can suppress tumor growth and is related to tumor proliferation; however, the mechanisms underlying these effects remain obscure. Methods Immunohistochemistry (IHC) was used to detect NDRG1 and p21 protein expression in colorectal cancer tissue, and clinical significance of NDRG1 was also analyzed. CCK-8 assay, colony formation assay, flow cytometry, and xenograft model were used to assess the effect of NDRG1 on tumor proliferation in vivo and in vitro. The mechanisms underlying the effect of NDRG1 were investigated using western blotting, immunofluorescence, immunoprecipitation, and ubiquitylation assay. Results NDRG1 was down-regulated in CRC tissues and correlated with tumor size and patient survival. NDRG1 inhibited tumor proliferation through increasing p21 expression via suppressing p21 ubiquitylation. NDRG1 and p21 had...

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authorSen Zhang ; Chaoran Yu ; Xiao Yang ; Hiju Hong ; Jiaoyang Lu ; Wenjun Hu ; Xiaohui Hao ; Shuchun Li ; Batuer Aikemu ; Guang Yang ; Zirui He ; Luyang Zhang ; Pei Xue ; Zhenghao Cai ; Junjun Ma ; Lu Zang ; Bo Feng ; Fei Yuan ; Jing Sun ; Minhua Zheng
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Abstract Background N-myc downstream-regulated gene 1 (NDRG1) has been shown to play a key role in tumor metastasis. Recent studies demonstrate that NDRG1 can suppress tumor growth and is related to tumor proliferation; however, the mechanisms underlying these effects remain obscure. Methods Immunohistochemistry (IHC) was used to detect NDRG1 and p21 protein expression in colorectal cancer tissue, and clinical significance of NDRG1 was also analyzed. CCK-8 assay, colony formation assay, flow cytometry, and xenograft model were used to assess the effect of NDRG1 on tumor proliferation in vivo and in vitro. The mechanisms underlying the effect of NDRG1 were investigated using western blotting, immunofluorescence, immunoprecipitation, and ubiquitylation assay. Results NDRG1 was down-regulated in CRC tissues and correlated with tumor size and patient survival. NDRG1 inhibited tumor proliferation through increasing p21 expression via suppressing p21 ubiquitylation. NDRG1 and p21 had...

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