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Erianin Induces Ferroptosis of Renal Cancer Stem Cells via Promoting ALOX12/P53 mRNA N6-methyladenosine Modification

Renal cell carcinoma (RCC) is the most common type of primary renal parenchymal malignancy in adults, with a high degree of malignancy and poor prognosis. Human renal cancer stem cells (HuRCSCs) are reported to be the main cause of drug resistance, metastasis, recurrence, and poor prognosis. Erianin...

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Autores principales: Shen, Hongliang, Geng, Zixiang, Nie, Xiaoli, Liu, Te
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9969579/
https://www.ncbi.nlm.nih.gov/pubmed/36860916
http://dx.doi.org/10.7150/jca.81027
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author Shen, Hongliang
Geng, Zixiang
Nie, Xiaoli
Liu, Te
author_facet Shen, Hongliang
Geng, Zixiang
Nie, Xiaoli
Liu, Te
author_sort Shen, Hongliang
collection PubMed
description Renal cell carcinoma (RCC) is the most common type of primary renal parenchymal malignancy in adults, with a high degree of malignancy and poor prognosis. Human renal cancer stem cells (HuRCSCs) are reported to be the main cause of drug resistance, metastasis, recurrence, and poor prognosis. Erianin is a low molecular-weight bibenzyl natural product extracted from Dendrobium chrysotoxum, which inhibits the in vitro and in vivo activity of a variety of cancer cells. However, the molecular mechanisms of Erianin's therapeutic effect on HuRCSCs are unknown. Here, we isolated CD44+/CD105+ HuRCSCs from patients with renal cell carcinoma. The experiments confirmed that Erianin significantly inhibited the proliferation, invasion, angiogenesis, and tumorigenesis of HuRCSCs, and induced oxidative stress injury and Fe(2+) accumulation. qRT-PCR and western blotting showed that Erianin significantly reduced the expression levels of cellular Ferroptosis protective factors, and upregulated the expression of METTL3 and downregulated that of FTO. Dot blotting results indicated that Erianin significantly upregulated the mRNA N6-methyladenosine (m6A) modification of HuRCSCs. The results of RNA immunoprecipitation-PCR also indicated that Erianin significantly enhanced the m6A modification level of the 3' untranslated region of ALOX12 and P53 mRNA in HuRCSCs, resulting in increased stability, prolonged half-life, and improved translation activity. In addition, clinical data analysis showed that the expression of FTO correlated negatively with adverse events in patient with renal cell carcinoma. Thus, this study suggested that Erianin can induce Ferroptosis in renal cancer stem cells by promoting N6-methyladenosine modification of ALOX12/P53 mRNA, ultimately achieving a therapeutic effect on renal cancer.
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spelling pubmed-99695792023-02-28 Erianin Induces Ferroptosis of Renal Cancer Stem Cells via Promoting ALOX12/P53 mRNA N6-methyladenosine Modification Shen, Hongliang Geng, Zixiang Nie, Xiaoli Liu, Te J Cancer Research Paper Renal cell carcinoma (RCC) is the most common type of primary renal parenchymal malignancy in adults, with a high degree of malignancy and poor prognosis. Human renal cancer stem cells (HuRCSCs) are reported to be the main cause of drug resistance, metastasis, recurrence, and poor prognosis. Erianin is a low molecular-weight bibenzyl natural product extracted from Dendrobium chrysotoxum, which inhibits the in vitro and in vivo activity of a variety of cancer cells. However, the molecular mechanisms of Erianin's therapeutic effect on HuRCSCs are unknown. Here, we isolated CD44+/CD105+ HuRCSCs from patients with renal cell carcinoma. The experiments confirmed that Erianin significantly inhibited the proliferation, invasion, angiogenesis, and tumorigenesis of HuRCSCs, and induced oxidative stress injury and Fe(2+) accumulation. qRT-PCR and western blotting showed that Erianin significantly reduced the expression levels of cellular Ferroptosis protective factors, and upregulated the expression of METTL3 and downregulated that of FTO. Dot blotting results indicated that Erianin significantly upregulated the mRNA N6-methyladenosine (m6A) modification of HuRCSCs. The results of RNA immunoprecipitation-PCR also indicated that Erianin significantly enhanced the m6A modification level of the 3' untranslated region of ALOX12 and P53 mRNA in HuRCSCs, resulting in increased stability, prolonged half-life, and improved translation activity. In addition, clinical data analysis showed that the expression of FTO correlated negatively with adverse events in patient with renal cell carcinoma. Thus, this study suggested that Erianin can induce Ferroptosis in renal cancer stem cells by promoting N6-methyladenosine modification of ALOX12/P53 mRNA, ultimately achieving a therapeutic effect on renal cancer. Ivyspring International Publisher 2023-01-22 /pmc/articles/PMC9969579/ /pubmed/36860916 http://dx.doi.org/10.7150/jca.81027 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Shen, Hongliang
Geng, Zixiang
Nie, Xiaoli
Liu, Te
Erianin Induces Ferroptosis of Renal Cancer Stem Cells via Promoting ALOX12/P53 mRNA N6-methyladenosine Modification
title Erianin Induces Ferroptosis of Renal Cancer Stem Cells via Promoting ALOX12/P53 mRNA N6-methyladenosine Modification
title_full Erianin Induces Ferroptosis of Renal Cancer Stem Cells via Promoting ALOX12/P53 mRNA N6-methyladenosine Modification
title_fullStr Erianin Induces Ferroptosis of Renal Cancer Stem Cells via Promoting ALOX12/P53 mRNA N6-methyladenosine Modification
title_full_unstemmed Erianin Induces Ferroptosis of Renal Cancer Stem Cells via Promoting ALOX12/P53 mRNA N6-methyladenosine Modification
title_short Erianin Induces Ferroptosis of Renal Cancer Stem Cells via Promoting ALOX12/P53 mRNA N6-methyladenosine Modification
title_sort erianin induces ferroptosis of renal cancer stem cells via promoting alox12/p53 mrna n6-methyladenosine modification
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9969579/
https://www.ncbi.nlm.nih.gov/pubmed/36860916
http://dx.doi.org/10.7150/jca.81027
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