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UBN2 promotes tumor progression via the Ras/MAPK pathway and predicts poor prognosis in colorectal cancer

BACKGROUND: Ubinuclein-2 (UBN2) is a nuclear protein that interacts with many transcription factors. The molecular role and mechanism of UBN2 in the development and progression of cancers, including colorectal cancer (CRC), is not well understood. The current study explored the role of UBN2 in the d...

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Autores principales: Zhao, Ya-li, Zhong, Shen-Rong, Zhang, Shi-Hong, Bi, Jia-Xin, Xiao, Zhi-Yuan, Wang, Shu-Yang, Jiao, Hong-Li, Zhang, Dan, Qiu, Jun-Feng, Zhang, Ling-Jie, Huang, Cheng-Mei, Chen, Xiao-Ling, Ding, Yan-Qing, Ye, Ya-Ping, Liang, Li, Liao, Wen-ting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511126/
https://www.ncbi.nlm.nih.gov/pubmed/31110467
http://dx.doi.org/10.1186/s12935-019-0848-4
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author Zhao, Ya-li
Zhong, Shen-Rong
Zhang, Shi-Hong
Bi, Jia-Xin
Xiao, Zhi-Yuan
Wang, Shu-Yang
Jiao, Hong-Li
Zhang, Dan
Qiu, Jun-Feng
Zhang, Ling-Jie
Huang, Cheng-Mei
Chen, Xiao-Ling
Ding, Yan-Qing
Ye, Ya-Ping
Liang, Li
Liao, Wen-ting
author_facet Zhao, Ya-li
Zhong, Shen-Rong
Zhang, Shi-Hong
Bi, Jia-Xin
Xiao, Zhi-Yuan
Wang, Shu-Yang
Jiao, Hong-Li
Zhang, Dan
Qiu, Jun-Feng
Zhang, Ling-Jie
Huang, Cheng-Mei
Chen, Xiao-Ling
Ding, Yan-Qing
Ye, Ya-Ping
Liang, Li
Liao, Wen-ting
author_sort Zhao, Ya-li
collection PubMed
description BACKGROUND: Ubinuclein-2 (UBN2) is a nuclear protein that interacts with many transcription factors. The molecular role and mechanism of UBN2 in the development and progression of cancers, including colorectal cancer (CRC), is not well understood. The current study explored the role of UBN2 in the development and progression CRC. METHODS: Oncomine network and The Cancer Genome Atlas (TCGA) database were downloaded and Gene Set Enrichment Analysis (GSEA) was performed to compare the UBN2′s expression between normal and tumor tissues, as well as the potential correlation of UBN2 expression with signaling pathways. Immunohistochemistry (IHC), qRT-PCR and Western blotting were performed to determine the expression of UBN2 in CRC tissues or cell lines. In vitro proliferation and invasion assays, and orthotopic mouse metastatic model were used to analyze the effect of UBN2 on the development and progression of CRC. RESULTS: The analysis of UBN2 expression using Oncomine network showed that UBN2 was upregulated in CRC tissues compared to matched adjacent normal intestinal epithelial tissues. IHC, qRT-PCR and Western blotting confirmed that UBN2 expression is higher in CRC tissues compared with matched adjacent normal intestinal epithelial tissues. In addition, analyses of TCGA data revealed that high UBN2 expression was associated with advanced stages of lymph node metastasis, distant metastasis, and short survival time in CRC patients. IHC showed that high UBN2 expression is correlated with advanced stages of CRC. Moreover, UBN2 is highly expressed in the liver metastatic lesions. Furthermore, knockdown of UBN2 inhibited the growth, invasiveness and metastasis of CRC cells via regulation of the Ras/MAPK signaling pathway. CONCLUSION: The current study demonstrates that UBN2 promotes tumor progression in CRC. UBN2 may be used as a promising biomarker for predicting the prognosis of CRC patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12935-019-0848-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-65111262019-05-20 UBN2 promotes tumor progression via the Ras/MAPK pathway and predicts poor prognosis in colorectal cancer Zhao, Ya-li Zhong, Shen-Rong Zhang, Shi-Hong Bi, Jia-Xin Xiao, Zhi-Yuan Wang, Shu-Yang Jiao, Hong-Li Zhang, Dan Qiu, Jun-Feng Zhang, Ling-Jie Huang, Cheng-Mei Chen, Xiao-Ling Ding, Yan-Qing Ye, Ya-Ping Liang, Li Liao, Wen-ting Cancer Cell Int Primary Research BACKGROUND: Ubinuclein-2 (UBN2) is a nuclear protein that interacts with many transcription factors. The molecular role and mechanism of UBN2 in the development and progression of cancers, including colorectal cancer (CRC), is not well understood. The current study explored the role of UBN2 in the development and progression CRC. METHODS: Oncomine network and The Cancer Genome Atlas (TCGA) database were downloaded and Gene Set Enrichment Analysis (GSEA) was performed to compare the UBN2′s expression between normal and tumor tissues, as well as the potential correlation of UBN2 expression with signaling pathways. Immunohistochemistry (IHC), qRT-PCR and Western blotting were performed to determine the expression of UBN2 in CRC tissues or cell lines. In vitro proliferation and invasion assays, and orthotopic mouse metastatic model were used to analyze the effect of UBN2 on the development and progression of CRC. RESULTS: The analysis of UBN2 expression using Oncomine network showed that UBN2 was upregulated in CRC tissues compared to matched adjacent normal intestinal epithelial tissues. IHC, qRT-PCR and Western blotting confirmed that UBN2 expression is higher in CRC tissues compared with matched adjacent normal intestinal epithelial tissues. In addition, analyses of TCGA data revealed that high UBN2 expression was associated with advanced stages of lymph node metastasis, distant metastasis, and short survival time in CRC patients. IHC showed that high UBN2 expression is correlated with advanced stages of CRC. Moreover, UBN2 is highly expressed in the liver metastatic lesions. Furthermore, knockdown of UBN2 inhibited the growth, invasiveness and metastasis of CRC cells via regulation of the Ras/MAPK signaling pathway. CONCLUSION: The current study demonstrates that UBN2 promotes tumor progression in CRC. UBN2 may be used as a promising biomarker for predicting the prognosis of CRC patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12935-019-0848-4) contains supplementary material, which is available to authorized users. BioMed Central 2019-05-10 /pmc/articles/PMC6511126/ /pubmed/31110467 http://dx.doi.org/10.1186/s12935-019-0848-4 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Primary Research
Zhao, Ya-li
Zhong, Shen-Rong
Zhang, Shi-Hong
Bi, Jia-Xin
Xiao, Zhi-Yuan
Wang, Shu-Yang
Jiao, Hong-Li
Zhang, Dan
Qiu, Jun-Feng
Zhang, Ling-Jie
Huang, Cheng-Mei
Chen, Xiao-Ling
Ding, Yan-Qing
Ye, Ya-Ping
Liang, Li
Liao, Wen-ting
UBN2 promotes tumor progression via the Ras/MAPK pathway and predicts poor prognosis in colorectal cancer
title UBN2 promotes tumor progression via the Ras/MAPK pathway and predicts poor prognosis in colorectal cancer
title_full UBN2 promotes tumor progression via the Ras/MAPK pathway and predicts poor prognosis in colorectal cancer
title_fullStr UBN2 promotes tumor progression via the Ras/MAPK pathway and predicts poor prognosis in colorectal cancer
title_full_unstemmed UBN2 promotes tumor progression via the Ras/MAPK pathway and predicts poor prognosis in colorectal cancer
title_short UBN2 promotes tumor progression via the Ras/MAPK pathway and predicts poor prognosis in colorectal cancer
title_sort ubn2 promotes tumor progression via the ras/mapk pathway and predicts poor prognosis in colorectal cancer
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511126/
https://www.ncbi.nlm.nih.gov/pubmed/31110467
http://dx.doi.org/10.1186/s12935-019-0848-4
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