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SIM2l attenuates resistance to hypoxia and tumor growth by transcriptional suppression of HIF1A in uterine cervical squamous cell carcinoma

Despite chemoradiotherapy being one of the most important modalities in advanced cervical cancer, there is a lack of both usable biomarkers to predict treatment outcome and of knowledge about the mechanism of refractoriness to the therapy. Here we identified a transcriptional factor Single-minded ho...

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Autores principales: Nakamura, Kanako, Komatsu, Masayuki, Chiwaki, Fumiko, Takeda, Takashi, Kobayashi, Yusuke, Banno, Kouji, Aoki, Daisuke, Yoshida, Teruhiko, Sasaki, Hiroki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674005/
https://www.ncbi.nlm.nih.gov/pubmed/29109451
http://dx.doi.org/10.1038/s41598-017-15261-4
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author Nakamura, Kanako
Komatsu, Masayuki
Chiwaki, Fumiko
Takeda, Takashi
Kobayashi, Yusuke
Banno, Kouji
Aoki, Daisuke
Yoshida, Teruhiko
Sasaki, Hiroki
author_facet Nakamura, Kanako
Komatsu, Masayuki
Chiwaki, Fumiko
Takeda, Takashi
Kobayashi, Yusuke
Banno, Kouji
Aoki, Daisuke
Yoshida, Teruhiko
Sasaki, Hiroki
author_sort Nakamura, Kanako
collection PubMed
description Despite chemoradiotherapy being one of the most important modalities in advanced cervical cancer, there is a lack of both usable biomarkers to predict treatment outcome and of knowledge about the mechanism of refractoriness to the therapy. Here we identified a transcriptional factor Single-minded homolog 2 (SIM2) as an independent predictive biomarker for uterine cervical squamous cell carcinoma (CvSCC). The retrospective study showed that high expression level of SIM2 was correlated to good survival in CvSCC patients. SIM2 knockdown in CvSCC cell lines showed resistance to hypoxia with increased expression of HIF1A and its target genes. Loss of SIM2 also caused growth promotion, resistance to ROS, and radiation in 3D culture. Furthermore, SIM2 knockdown suppressed tumor growth with increased HIF-1α expression and angiogenesis in vivo. On the other hand, SIM2 long isoform (SIM2l)-overexpressed cells had contrary results, indicating the long isoform plays a key role for maintenance of these phenotypes. These data indicated that SIM2l has a potential to be precision medicine for CvSCC patients and that anti-angiogenesis therapy might be usable for SIM2l(Low) poor survivors.
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spelling pubmed-56740052017-11-15 SIM2l attenuates resistance to hypoxia and tumor growth by transcriptional suppression of HIF1A in uterine cervical squamous cell carcinoma Nakamura, Kanako Komatsu, Masayuki Chiwaki, Fumiko Takeda, Takashi Kobayashi, Yusuke Banno, Kouji Aoki, Daisuke Yoshida, Teruhiko Sasaki, Hiroki Sci Rep Article Despite chemoradiotherapy being one of the most important modalities in advanced cervical cancer, there is a lack of both usable biomarkers to predict treatment outcome and of knowledge about the mechanism of refractoriness to the therapy. Here we identified a transcriptional factor Single-minded homolog 2 (SIM2) as an independent predictive biomarker for uterine cervical squamous cell carcinoma (CvSCC). The retrospective study showed that high expression level of SIM2 was correlated to good survival in CvSCC patients. SIM2 knockdown in CvSCC cell lines showed resistance to hypoxia with increased expression of HIF1A and its target genes. Loss of SIM2 also caused growth promotion, resistance to ROS, and radiation in 3D culture. Furthermore, SIM2 knockdown suppressed tumor growth with increased HIF-1α expression and angiogenesis in vivo. On the other hand, SIM2 long isoform (SIM2l)-overexpressed cells had contrary results, indicating the long isoform plays a key role for maintenance of these phenotypes. These data indicated that SIM2l has a potential to be precision medicine for CvSCC patients and that anti-angiogenesis therapy might be usable for SIM2l(Low) poor survivors. Nature Publishing Group UK 2017-11-06 /pmc/articles/PMC5674005/ /pubmed/29109451 http://dx.doi.org/10.1038/s41598-017-15261-4 Text en © The Author(s) 2017 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
Nakamura, Kanako
Komatsu, Masayuki
Chiwaki, Fumiko
Takeda, Takashi
Kobayashi, Yusuke
Banno, Kouji
Aoki, Daisuke
Yoshida, Teruhiko
Sasaki, Hiroki
SIM2l attenuates resistance to hypoxia and tumor growth by transcriptional suppression of HIF1A in uterine cervical squamous cell carcinoma
title SIM2l attenuates resistance to hypoxia and tumor growth by transcriptional suppression of HIF1A in uterine cervical squamous cell carcinoma
title_full SIM2l attenuates resistance to hypoxia and tumor growth by transcriptional suppression of HIF1A in uterine cervical squamous cell carcinoma
title_fullStr SIM2l attenuates resistance to hypoxia and tumor growth by transcriptional suppression of HIF1A in uterine cervical squamous cell carcinoma
title_full_unstemmed SIM2l attenuates resistance to hypoxia and tumor growth by transcriptional suppression of HIF1A in uterine cervical squamous cell carcinoma
title_short SIM2l attenuates resistance to hypoxia and tumor growth by transcriptional suppression of HIF1A in uterine cervical squamous cell carcinoma
title_sort sim2l attenuates resistance to hypoxia and tumor growth by transcriptional suppression of hif1a in uterine cervical squamous cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674005/
https://www.ncbi.nlm.nih.gov/pubmed/29109451
http://dx.doi.org/10.1038/s41598-017-15261-4
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