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Silencing circFTO inhibits malignant phenotype through modulating DUSP4 expression in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is the most diagnosed malignancy in kidney. Studies on the role of circular RNAs in kidney cancer are increasing. In this study, we employed high throughput sequencing and tissue micro array to detect and verify one of the key circular RNAs, circFTO, in ccRCC....

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Autores principales: Yang, Chen, Zang, Yiwen, Wu, Siqi, Zhou, Quan, Ou, Yuxi, Ding, Qiang, Wang, Hao, Xiong, Zuquan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9489864/
https://www.ncbi.nlm.nih.gov/pubmed/36127345
http://dx.doi.org/10.1038/s41420-022-01138-7
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author Yang, Chen
Zang, Yiwen
Wu, Siqi
Zhou, Quan
Ou, Yuxi
Ding, Qiang
Wang, Hao
Xiong, Zuquan
author_facet Yang, Chen
Zang, Yiwen
Wu, Siqi
Zhou, Quan
Ou, Yuxi
Ding, Qiang
Wang, Hao
Xiong, Zuquan
author_sort Yang, Chen
collection PubMed
description Clear cell renal cell carcinoma (ccRCC) is the most diagnosed malignancy in kidney. Studies on the role of circular RNAs in kidney cancer are increasing. In this study, we employed high throughput sequencing and tissue micro array to detect and verify one of the key circular RNAs, circFTO, in ccRCC. The effect of circFTO on the proliferation and invasiveness of ccRCC cells and the corresponding mechanism were studied both in vitro and in vivo via multiple methods. We confirmed that circFTO was up regulated in ccRCC and correlated with a more aggressive phenotype. The up regulated circFTO could sponge and block the function of miR-514b-3p, a reported tumor suppressor, and caused overexpression of DUSP4. DUSP4 was found to lead to KRAS/ERK pathway activation, increased epithelial-mesenchymal transition (EMT) and inhibition of autophagy in ccRCC cells, which in the end boosted the proliferation and invasiveness of ccRCC. We thus concluded that circFTO/miR-514b-3p/DUSP4 axis may play an important role in ccRCC development and could be a potential biomarker and therapeutic target.
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spelling pubmed-94898642022-09-22 Silencing circFTO inhibits malignant phenotype through modulating DUSP4 expression in clear cell renal cell carcinoma Yang, Chen Zang, Yiwen Wu, Siqi Zhou, Quan Ou, Yuxi Ding, Qiang Wang, Hao Xiong, Zuquan Cell Death Discov Article Clear cell renal cell carcinoma (ccRCC) is the most diagnosed malignancy in kidney. Studies on the role of circular RNAs in kidney cancer are increasing. In this study, we employed high throughput sequencing and tissue micro array to detect and verify one of the key circular RNAs, circFTO, in ccRCC. The effect of circFTO on the proliferation and invasiveness of ccRCC cells and the corresponding mechanism were studied both in vitro and in vivo via multiple methods. We confirmed that circFTO was up regulated in ccRCC and correlated with a more aggressive phenotype. The up regulated circFTO could sponge and block the function of miR-514b-3p, a reported tumor suppressor, and caused overexpression of DUSP4. DUSP4 was found to lead to KRAS/ERK pathway activation, increased epithelial-mesenchymal transition (EMT) and inhibition of autophagy in ccRCC cells, which in the end boosted the proliferation and invasiveness of ccRCC. We thus concluded that circFTO/miR-514b-3p/DUSP4 axis may play an important role in ccRCC development and could be a potential biomarker and therapeutic target. Nature Publishing Group UK 2022-09-20 /pmc/articles/PMC9489864/ /pubmed/36127345 http://dx.doi.org/10.1038/s41420-022-01138-7 Text en © The Author(s) 2022, corrected publication 2022 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
Yang, Chen
Zang, Yiwen
Wu, Siqi
Zhou, Quan
Ou, Yuxi
Ding, Qiang
Wang, Hao
Xiong, Zuquan
Silencing circFTO inhibits malignant phenotype through modulating DUSP4 expression in clear cell renal cell carcinoma
title Silencing circFTO inhibits malignant phenotype through modulating DUSP4 expression in clear cell renal cell carcinoma
title_full Silencing circFTO inhibits malignant phenotype through modulating DUSP4 expression in clear cell renal cell carcinoma
title_fullStr Silencing circFTO inhibits malignant phenotype through modulating DUSP4 expression in clear cell renal cell carcinoma
title_full_unstemmed Silencing circFTO inhibits malignant phenotype through modulating DUSP4 expression in clear cell renal cell carcinoma
title_short Silencing circFTO inhibits malignant phenotype through modulating DUSP4 expression in clear cell renal cell carcinoma
title_sort silencing circfto inhibits malignant phenotype through modulating dusp4 expression in clear cell renal cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9489864/
https://www.ncbi.nlm.nih.gov/pubmed/36127345
http://dx.doi.org/10.1038/s41420-022-01138-7
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