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The miR-532-E2F1 feedback loop contributes to gastric cancer progression

Gastric cancer (GC) ranks fourth in incidence and mortality worldwide, ascertaining the pathogenesis of GC is crucial for its treatment. E2F1, which regulates the transcription of genes encoding proteins involved in DNA repair, DNA replication, mitosis and survival of cancer patients, functions as a...

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Autores principales: Gao, Shanting, Bu, Xiaomin, Gao, Yongyue, Bao, Zengtao, Shi, Wenchao, Luan, Lipeng, Chen, Huiyu, Zhang, Baoming, Tian, Qingshui, Guan, Wenxian, Yang, Liuqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018701/
https://www.ncbi.nlm.nih.gov/pubmed/35440106
http://dx.doi.org/10.1038/s41419-022-04832-7
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author Gao, Shanting
Bu, Xiaomin
Gao, Yongyue
Bao, Zengtao
Shi, Wenchao
Luan, Lipeng
Chen, Huiyu
Zhang, Baoming
Tian, Qingshui
Guan, Wenxian
Yang, Liuqing
author_facet Gao, Shanting
Bu, Xiaomin
Gao, Yongyue
Bao, Zengtao
Shi, Wenchao
Luan, Lipeng
Chen, Huiyu
Zhang, Baoming
Tian, Qingshui
Guan, Wenxian
Yang, Liuqing
author_sort Gao, Shanting
collection PubMed
description Gastric cancer (GC) ranks fourth in incidence and mortality worldwide, ascertaining the pathogenesis of GC is crucial for its treatment. E2F1, which regulates the transcription of genes encoding proteins involved in DNA repair, DNA replication, mitosis and survival of cancer patients, functions as a key regulator in GC progression. However, the underneath mechanism of these processes is not fully elucidated. Here, TCGA database analysis, microarray immunohistochemical technique and western blot showed that E2F1 was highly upregulated in clinical GC tissues and correlated with tumor malignancy. In vitro and in vivo assays confirmed the oncogenic function of E2F1. MiR-532 was decreased and negatively correlated with E2F1 in GC tissues. MiR-532 directly targeted and inhibited E2F1 expression, leading to the decrease of ASK1 and elevation of TXNIP, and affected proliferation, cell cycle, apoptosis and DNA damage in vitro and tumor growth in vivo. Moreover, E2F1 serves as a transcriptional repressor to suppress miR-532 expression and a double-negative feedback loop was formed between them. This study demonstrates the significant roles of the E2F1-miR-532 double-negative feedback loop in GC progression and may represent a potential target for GC therapy.
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spelling pubmed-90187012022-04-28 The miR-532-E2F1 feedback loop contributes to gastric cancer progression Gao, Shanting Bu, Xiaomin Gao, Yongyue Bao, Zengtao Shi, Wenchao Luan, Lipeng Chen, Huiyu Zhang, Baoming Tian, Qingshui Guan, Wenxian Yang, Liuqing Cell Death Dis Article Gastric cancer (GC) ranks fourth in incidence and mortality worldwide, ascertaining the pathogenesis of GC is crucial for its treatment. E2F1, which regulates the transcription of genes encoding proteins involved in DNA repair, DNA replication, mitosis and survival of cancer patients, functions as a key regulator in GC progression. However, the underneath mechanism of these processes is not fully elucidated. Here, TCGA database analysis, microarray immunohistochemical technique and western blot showed that E2F1 was highly upregulated in clinical GC tissues and correlated with tumor malignancy. In vitro and in vivo assays confirmed the oncogenic function of E2F1. MiR-532 was decreased and negatively correlated with E2F1 in GC tissues. MiR-532 directly targeted and inhibited E2F1 expression, leading to the decrease of ASK1 and elevation of TXNIP, and affected proliferation, cell cycle, apoptosis and DNA damage in vitro and tumor growth in vivo. Moreover, E2F1 serves as a transcriptional repressor to suppress miR-532 expression and a double-negative feedback loop was formed between them. This study demonstrates the significant roles of the E2F1-miR-532 double-negative feedback loop in GC progression and may represent a potential target for GC therapy. Nature Publishing Group UK 2022-04-19 /pmc/articles/PMC9018701/ /pubmed/35440106 http://dx.doi.org/10.1038/s41419-022-04832-7 Text en © The Author(s) 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
Gao, Shanting
Bu, Xiaomin
Gao, Yongyue
Bao, Zengtao
Shi, Wenchao
Luan, Lipeng
Chen, Huiyu
Zhang, Baoming
Tian, Qingshui
Guan, Wenxian
Yang, Liuqing
The miR-532-E2F1 feedback loop contributes to gastric cancer progression
title The miR-532-E2F1 feedback loop contributes to gastric cancer progression
title_full The miR-532-E2F1 feedback loop contributes to gastric cancer progression
title_fullStr The miR-532-E2F1 feedback loop contributes to gastric cancer progression
title_full_unstemmed The miR-532-E2F1 feedback loop contributes to gastric cancer progression
title_short The miR-532-E2F1 feedback loop contributes to gastric cancer progression
title_sort mir-532-e2f1 feedback loop contributes to gastric cancer progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018701/
https://www.ncbi.nlm.nih.gov/pubmed/35440106
http://dx.doi.org/10.1038/s41419-022-04832-7
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