SNX16 activates c‐Myc signaling by inhibiting ubiquitin‐mediated proteasomal degradation of eEF1A2 in colorectal cancer development

Sorting nexin 16 (SNX16), a member of the sorting nexin family, has been implicated in tumor development. However, the function of SNX16 has not yet been investigated in colorectal cancer (CRC). Here, we showed that SNX16 expression was significantly upregulated in CRC tissues compared with normal c...

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Main Authors: Zhiyong Shen, Yongsheng Li, Yuan Fang, Mingdao Lin, Xiaochuang Feng, Zhenkang Li, Yizhi Zhan, Yuechen Liu, Tingyu Mou, Xiaoliang Lan, Yanan Wang, Guoxin Li, Jiping Wang, Haijun Deng
Format: Article
Language:English
Published: Wiley 2020-02-01
Series:Molecular Oncology
Subjects:
Online Access:https://doi.org/10.1002/1878-0261.12626
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author Zhiyong Shen
Yongsheng Li
Yuan Fang
Mingdao Lin
Xiaochuang Feng
Zhenkang Li
Yizhi Zhan
Yuechen Liu
Tingyu Mou
Xiaoliang Lan
Yanan Wang
Guoxin Li
Jiping Wang
Haijun Deng
author_facet Zhiyong Shen
Yongsheng Li
Yuan Fang
Mingdao Lin
Xiaochuang Feng
Zhenkang Li
Yizhi Zhan
Yuechen Liu
Tingyu Mou
Xiaoliang Lan
Yanan Wang
Guoxin Li
Jiping Wang
Haijun Deng
author_sort Zhiyong Shen
collection DOAJ
description Sorting nexin 16 (SNX16), a member of the sorting nexin family, has been implicated in tumor development. However, the function of SNX16 has not yet been investigated in colorectal cancer (CRC). Here, we showed that SNX16 expression was significantly upregulated in CRC tissues compared with normal counterparts. Upregulated mRNA levels of SNX16 predicted poor survival of CRC patients. Functional experiments showed that SNX16 could promote CRC cells growth both in vitro and in vivo. Knockdown of SNX16 induced cell cycle arrest and apoptosis, whereas ectopic overexpression of SNX16 had the opposite effects. Mechanistically, SNX16‐eukaryotic translation elongation factor 1A2 (eEF1A2) interaction could inhibit the degradation and ubiquitination of eEF1A2, followed by activation of downstream c‐Myc signaling. Our study unveiled that the SNX16/eEF1A2/c‐Myc signaling axis could promote colorectal tumorigenesis and SNX16 might potentially serve as a novel biomarker for the diagnosis and an intervention of CRC.
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spelling doaj.art-aab6671c43c545d29bc541cb732b415b2023-05-26T04:31:40ZengWileyMolecular Oncology1574-78911878-02612020-02-0114238740610.1002/1878-0261.12626SNX16 activates c‐Myc signaling by inhibiting ubiquitin‐mediated proteasomal degradation of eEF1A2 in colorectal cancer developmentZhiyong Shen0Yongsheng Li1Yuan Fang2Mingdao Lin3Xiaochuang Feng4Zhenkang Li5Yizhi Zhan6Yuechen Liu7Tingyu Mou8Xiaoliang Lan9Yanan Wang10Guoxin Li11Jiping Wang12Haijun Deng13Department of General Surgery Nanfang Hospital Southern Medical University Guangzhou ChinaDepartment of General Surgery Nanfang Hospital Southern Medical University Guangzhou ChinaDepartment of Radiation Oncology Nanfang Hospital Southern Medical University Guangzhou ChinaDepartment of General Surgery Nanfang Hospital Southern Medical University Guangzhou ChinaDepartment of General Surgery Nanfang Hospital Southern Medical University Guangzhou ChinaDepartment of General Surgery Nanfang Hospital Southern Medical University Guangzhou ChinaDepartment of Pathology Nanfang Hospital Southern Medical University Guangzhou ChinaDepartment of General Surgery Nanfang Hospital Southern Medical University Guangzhou ChinaDepartment of General Surgery Nanfang Hospital Southern Medical University Guangzhou ChinaDepartment of General Surgery Nanfang Hospital Southern Medical University Guangzhou ChinaDepartment of General Surgery Nanfang Hospital Southern Medical University Guangzhou ChinaDepartment of General Surgery Nanfang Hospital Southern Medical University Guangzhou ChinaDivision of Surgical Oncology Department of Surgery Brigham and Women's Hospital Harvard Medical School Boston MA USADepartment of General Surgery Nanfang Hospital Southern Medical University Guangzhou ChinaSorting nexin 16 (SNX16), a member of the sorting nexin family, has been implicated in tumor development. However, the function of SNX16 has not yet been investigated in colorectal cancer (CRC). Here, we showed that SNX16 expression was significantly upregulated in CRC tissues compared with normal counterparts. Upregulated mRNA levels of SNX16 predicted poor survival of CRC patients. Functional experiments showed that SNX16 could promote CRC cells growth both in vitro and in vivo. Knockdown of SNX16 induced cell cycle arrest and apoptosis, whereas ectopic overexpression of SNX16 had the opposite effects. Mechanistically, SNX16‐eukaryotic translation elongation factor 1A2 (eEF1A2) interaction could inhibit the degradation and ubiquitination of eEF1A2, followed by activation of downstream c‐Myc signaling. Our study unveiled that the SNX16/eEF1A2/c‐Myc signaling axis could promote colorectal tumorigenesis and SNX16 might potentially serve as a novel biomarker for the diagnosis and an intervention of CRC.https://doi.org/10.1002/1878-0261.12626cell proliferationc‐Myccolorectal cancereEF1A2SNX16
spellingShingle Zhiyong Shen
Yongsheng Li
Yuan Fang
Mingdao Lin
Xiaochuang Feng
Zhenkang Li
Yizhi Zhan
Yuechen Liu
Tingyu Mou
Xiaoliang Lan
Yanan Wang
Guoxin Li
Jiping Wang
Haijun Deng
SNX16 activates c‐Myc signaling by inhibiting ubiquitin‐mediated proteasomal degradation of eEF1A2 in colorectal cancer development
Molecular Oncology
cell proliferation
c‐Myc
colorectal cancer
eEF1A2
SNX16
title SNX16 activates c‐Myc signaling by inhibiting ubiquitin‐mediated proteasomal degradation of eEF1A2 in colorectal cancer development
title_full SNX16 activates c‐Myc signaling by inhibiting ubiquitin‐mediated proteasomal degradation of eEF1A2 in colorectal cancer development
title_fullStr SNX16 activates c‐Myc signaling by inhibiting ubiquitin‐mediated proteasomal degradation of eEF1A2 in colorectal cancer development
title_full_unstemmed SNX16 activates c‐Myc signaling by inhibiting ubiquitin‐mediated proteasomal degradation of eEF1A2 in colorectal cancer development
title_short SNX16 activates c‐Myc signaling by inhibiting ubiquitin‐mediated proteasomal degradation of eEF1A2 in colorectal cancer development
title_sort snx16 activates c myc signaling by inhibiting ubiquitin mediated proteasomal degradation of eef1a2 in colorectal cancer development
topic cell proliferation
c‐Myc
colorectal cancer
eEF1A2
SNX16
url https://doi.org/10.1002/1878-0261.12626
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