Long noncoding RNA SNHG12 promotes tumour progression and sunitinib resistance by upregulating CDCA3 in renal cell carcinoma

Renal cell carcinoma (RCC) is one of the most frequently observed malignant tumours in the urinary system and targeted drug resistance is quite common in RCC. Long noncoding RNA SNHG12 (lncRNA SNHG12) has emerged as a key molecule in numerous human cancers, but its functions in renal cell carcinoma...

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Autores principales: Liu, Yuenan, Cheng, Gong, Huang, Ziwei, Bao, Lin, Liu, Jingchong, Wang, Cheng, Xiong, Zhiyong, Zhou, Lijie, Xu, Tianbo, Liu, Di, Yang, Hongmei, Chen, Ke, Zhang, Xiaoping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343829/
https://www.ncbi.nlm.nih.gov/pubmed/32641718
http://dx.doi.org/10.1038/s41419-020-2713-8
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author Liu, Yuenan
Cheng, Gong
Huang, Ziwei
Bao, Lin
Liu, Jingchong
Wang, Cheng
Xiong, Zhiyong
Zhou, Lijie
Xu, Tianbo
Liu, Di
Yang, Hongmei
Chen, Ke
Zhang, Xiaoping
author_facet Liu, Yuenan
Cheng, Gong
Huang, Ziwei
Bao, Lin
Liu, Jingchong
Wang, Cheng
Xiong, Zhiyong
Zhou, Lijie
Xu, Tianbo
Liu, Di
Yang, Hongmei
Chen, Ke
Zhang, Xiaoping
author_sort Liu, Yuenan
collection PubMed
description Renal cell carcinoma (RCC) is one of the most frequently observed malignant tumours in the urinary system and targeted drug resistance is quite common in RCC. Long noncoding RNA SNHG12 (lncRNA SNHG12) has emerged as a key molecule in numerous human cancers, but its functions in renal cell carcinoma (RCC) sunitinib resistance remain unclear. In this study, we found SNHG12 was highly expressed in RCC tissues and in sunitinib-resistant RCC cells and was associated with a poor clinical prognosis. SNHG12 promoted RCC proliferation, migration, invasion and sunitinib resistance via CDCA3 in vitro. Mechanically, SNHG12 bound to SP1 and prevented the ubiquitylation-dependent proteolysis of SP1. Stabilised SP1 bound to a specific region in the promoter of CDCA3 and increased CDCA3 expression. Furthermore, in vivo experiments showed that SNHG12 increased tumour growth and that knocking down SNHG12 could reverse RCC sunitinib resistance. Our study revealed that the lncRNA SNHG12/SP1/CDCA3 axis promoted RCC progression and sunitinib resistance, which could provide a new therapeutic target for sunitinib-resistant RCC.
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spelling pubmed-73438292020-07-13 Long noncoding RNA SNHG12 promotes tumour progression and sunitinib resistance by upregulating CDCA3 in renal cell carcinoma Liu, Yuenan Cheng, Gong Huang, Ziwei Bao, Lin Liu, Jingchong Wang, Cheng Xiong, Zhiyong Zhou, Lijie Xu, Tianbo Liu, Di Yang, Hongmei Chen, Ke Zhang, Xiaoping Cell Death Dis Article Renal cell carcinoma (RCC) is one of the most frequently observed malignant tumours in the urinary system and targeted drug resistance is quite common in RCC. Long noncoding RNA SNHG12 (lncRNA SNHG12) has emerged as a key molecule in numerous human cancers, but its functions in renal cell carcinoma (RCC) sunitinib resistance remain unclear. In this study, we found SNHG12 was highly expressed in RCC tissues and in sunitinib-resistant RCC cells and was associated with a poor clinical prognosis. SNHG12 promoted RCC proliferation, migration, invasion and sunitinib resistance via CDCA3 in vitro. Mechanically, SNHG12 bound to SP1 and prevented the ubiquitylation-dependent proteolysis of SP1. Stabilised SP1 bound to a specific region in the promoter of CDCA3 and increased CDCA3 expression. Furthermore, in vivo experiments showed that SNHG12 increased tumour growth and that knocking down SNHG12 could reverse RCC sunitinib resistance. Our study revealed that the lncRNA SNHG12/SP1/CDCA3 axis promoted RCC progression and sunitinib resistance, which could provide a new therapeutic target for sunitinib-resistant RCC. Nature Publishing Group UK 2020-07-08 /pmc/articles/PMC7343829/ /pubmed/32641718 http://dx.doi.org/10.1038/s41419-020-2713-8 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Liu, Yuenan
Cheng, Gong
Huang, Ziwei
Bao, Lin
Liu, Jingchong
Wang, Cheng
Xiong, Zhiyong
Zhou, Lijie
Xu, Tianbo
Liu, Di
Yang, Hongmei
Chen, Ke
Zhang, Xiaoping
Long noncoding RNA SNHG12 promotes tumour progression and sunitinib resistance by upregulating CDCA3 in renal cell carcinoma
title Long noncoding RNA SNHG12 promotes tumour progression and sunitinib resistance by upregulating CDCA3 in renal cell carcinoma
title_full Long noncoding RNA SNHG12 promotes tumour progression and sunitinib resistance by upregulating CDCA3 in renal cell carcinoma
title_fullStr Long noncoding RNA SNHG12 promotes tumour progression and sunitinib resistance by upregulating CDCA3 in renal cell carcinoma
title_full_unstemmed Long noncoding RNA SNHG12 promotes tumour progression and sunitinib resistance by upregulating CDCA3 in renal cell carcinoma
title_short Long noncoding RNA SNHG12 promotes tumour progression and sunitinib resistance by upregulating CDCA3 in renal cell carcinoma
title_sort long noncoding rna snhg12 promotes tumour progression and sunitinib resistance by upregulating cdca3 in renal cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343829/
https://www.ncbi.nlm.nih.gov/pubmed/32641718
http://dx.doi.org/10.1038/s41419-020-2713-8
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