circPTPN12 promotes the progression and sunitinib resistance of renal cancer via hnRNPM/IL-6/STAT3 pathway

Renal cell carcinoma (RCC) is characterized by the difficulties in early diagnosis and the propensity to metastases. For advanced RCC, sunitinib targeted therapy is the clinically recommended first-line drug and the major challenge of sunitinib treatment is adaptive resistance. Therefore, it is impe...

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Autores principales: Shou, Yi, Yue, Changjie, Wang, Qi, Liu, Jingchong, Xu, Jiaju, Miao, Qi, Liu, Di, Yang, Hongmei, Liu, Yuenan, Zhang, Xiaoping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10066201/
https://www.ncbi.nlm.nih.gov/pubmed/37002206
http://dx.doi.org/10.1038/s41419-023-05717-z
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author Shou, Yi
Yue, Changjie
Wang, Qi
Liu, Jingchong
Xu, Jiaju
Miao, Qi
Liu, Di
Yang, Hongmei
Liu, Yuenan
Zhang, Xiaoping
author_facet Shou, Yi
Yue, Changjie
Wang, Qi
Liu, Jingchong
Xu, Jiaju
Miao, Qi
Liu, Di
Yang, Hongmei
Liu, Yuenan
Zhang, Xiaoping
author_sort Shou, Yi
collection PubMed
description Renal cell carcinoma (RCC) is characterized by the difficulties in early diagnosis and the propensity to metastases. For advanced RCC, sunitinib targeted therapy is the clinically recommended first-line drug and the major challenge of sunitinib treatment is adaptive resistance. Therefore, it is imperative to research the mechanisms underlying sunitinib resistance. In this study, we discovered that circPTPN12 was highly expressed in RCC tissues and was associated with poorer clinical outcomes. circPTPN12 could promote the proliferation, migration, invasion, and sunitinib resistance of RCC cells. Mechanistically, circPTPN12 was found to form a complex with hnRNPM, which was involved in the regulation of mRNA processing. The combination with circPTPN12 enhanced the ability of hnRNPM to maintain the stability of IL-6 mRNA and further activated the STAT3 signaling pathway. The study revealed that circPTPN12/hnRNPM/IL-6/STAT3 axis promoted RCC progression and sunitinib resistance, which might be a promising therapeutic target for relieving sunitinib resistance in RCC.
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spelling pubmed-100662012023-04-02 circPTPN12 promotes the progression and sunitinib resistance of renal cancer via hnRNPM/IL-6/STAT3 pathway Shou, Yi Yue, Changjie Wang, Qi Liu, Jingchong Xu, Jiaju Miao, Qi Liu, Di Yang, Hongmei Liu, Yuenan Zhang, Xiaoping Cell Death Dis Article Renal cell carcinoma (RCC) is characterized by the difficulties in early diagnosis and the propensity to metastases. For advanced RCC, sunitinib targeted therapy is the clinically recommended first-line drug and the major challenge of sunitinib treatment is adaptive resistance. Therefore, it is imperative to research the mechanisms underlying sunitinib resistance. In this study, we discovered that circPTPN12 was highly expressed in RCC tissues and was associated with poorer clinical outcomes. circPTPN12 could promote the proliferation, migration, invasion, and sunitinib resistance of RCC cells. Mechanistically, circPTPN12 was found to form a complex with hnRNPM, which was involved in the regulation of mRNA processing. The combination with circPTPN12 enhanced the ability of hnRNPM to maintain the stability of IL-6 mRNA and further activated the STAT3 signaling pathway. The study revealed that circPTPN12/hnRNPM/IL-6/STAT3 axis promoted RCC progression and sunitinib resistance, which might be a promising therapeutic target for relieving sunitinib resistance in RCC. Nature Publishing Group UK 2023-03-31 /pmc/articles/PMC10066201/ /pubmed/37002206 http://dx.doi.org/10.1038/s41419-023-05717-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Shou, Yi
Yue, Changjie
Wang, Qi
Liu, Jingchong
Xu, Jiaju
Miao, Qi
Liu, Di
Yang, Hongmei
Liu, Yuenan
Zhang, Xiaoping
circPTPN12 promotes the progression and sunitinib resistance of renal cancer via hnRNPM/IL-6/STAT3 pathway
title circPTPN12 promotes the progression and sunitinib resistance of renal cancer via hnRNPM/IL-6/STAT3 pathway
title_full circPTPN12 promotes the progression and sunitinib resistance of renal cancer via hnRNPM/IL-6/STAT3 pathway
title_fullStr circPTPN12 promotes the progression and sunitinib resistance of renal cancer via hnRNPM/IL-6/STAT3 pathway
title_full_unstemmed circPTPN12 promotes the progression and sunitinib resistance of renal cancer via hnRNPM/IL-6/STAT3 pathway
title_short circPTPN12 promotes the progression and sunitinib resistance of renal cancer via hnRNPM/IL-6/STAT3 pathway
title_sort circptpn12 promotes the progression and sunitinib resistance of renal cancer via hnrnpm/il-6/stat3 pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10066201/
https://www.ncbi.nlm.nih.gov/pubmed/37002206
http://dx.doi.org/10.1038/s41419-023-05717-z
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