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hTERT Promotes CRC Proliferation and Migration by Recruiting YBX1 to Increase NRF2 Expression

High human telomerase reverse transcriptase (hTERT) expression is related to severe Colorectal Cancer (CRC) progression and negatively related to CRC patient survival. Previous studies have revealed that hTERT can reduce cancer cellular reactive oxygen species (ROS) levels and accelerate cancer prog...

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Autores principales: Gong, Chunli, Yang, Huan, Wang, Sumin, Liu, Jiao, Li, Zhibin, Hu, Yiyang, Chen, Yang, Huang, Yu, Luo, Qiang, Wu, Yuyun, Liu, En, Xiao, Yufeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165255/
https://www.ncbi.nlm.nih.gov/pubmed/34079797
http://dx.doi.org/10.3389/fcell.2021.658101
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author Gong, Chunli
Yang, Huan
Wang, Sumin
Liu, Jiao
Li, Zhibin
Hu, Yiyang
Chen, Yang
Huang, Yu
Luo, Qiang
Wu, Yuyun
Liu, En
Xiao, Yufeng
author_facet Gong, Chunli
Yang, Huan
Wang, Sumin
Liu, Jiao
Li, Zhibin
Hu, Yiyang
Chen, Yang
Huang, Yu
Luo, Qiang
Wu, Yuyun
Liu, En
Xiao, Yufeng
author_sort Gong, Chunli
collection PubMed
description High human telomerase reverse transcriptase (hTERT) expression is related to severe Colorectal Cancer (CRC) progression and negatively related to CRC patient survival. Previous studies have revealed that hTERT can reduce cancer cellular reactive oxygen species (ROS) levels and accelerate cancer progression; however, the mechanism remains poorly understood. NFE2-related factor 2 (NRF2) is a molecule that plays a significant role in regulating cellular ROS homeostasis, but whether there is a correlation between hTERT and NRF2 remains unclear. Here, we showed that hTERT increases CRC proliferation and migration by inducing NRF2 upregulation. We further found that hTERT increases NRF2 expression at both the mRNA and protein levels. Our data also revealed that hTERT primarily upregulates NRF2 by increasing NRF2 promoter activity rather than by regulating NRF2 mRNA or protein stability. Using DNA pull-down/MS analysis, we found that hTERT can recruit YBX1 to upregulate NRF2 promoter activity. We also found that hTERT/YBX1 may localize to the P2 region of the NRF2 promoter. Taken together, our results demonstrate that hTERT facilitates CRC proliferation and migration by upregulating NRF2 expression through the recruitment of the transcription factor YBX1 to activate the NRF2 promoter. These results provide a new theoretical basis for CRC treatment.
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spelling pubmed-81652552021-06-01 hTERT Promotes CRC Proliferation and Migration by Recruiting YBX1 to Increase NRF2 Expression Gong, Chunli Yang, Huan Wang, Sumin Liu, Jiao Li, Zhibin Hu, Yiyang Chen, Yang Huang, Yu Luo, Qiang Wu, Yuyun Liu, En Xiao, Yufeng Front Cell Dev Biol Cell and Developmental Biology High human telomerase reverse transcriptase (hTERT) expression is related to severe Colorectal Cancer (CRC) progression and negatively related to CRC patient survival. Previous studies have revealed that hTERT can reduce cancer cellular reactive oxygen species (ROS) levels and accelerate cancer progression; however, the mechanism remains poorly understood. NFE2-related factor 2 (NRF2) is a molecule that plays a significant role in regulating cellular ROS homeostasis, but whether there is a correlation between hTERT and NRF2 remains unclear. Here, we showed that hTERT increases CRC proliferation and migration by inducing NRF2 upregulation. We further found that hTERT increases NRF2 expression at both the mRNA and protein levels. Our data also revealed that hTERT primarily upregulates NRF2 by increasing NRF2 promoter activity rather than by regulating NRF2 mRNA or protein stability. Using DNA pull-down/MS analysis, we found that hTERT can recruit YBX1 to upregulate NRF2 promoter activity. We also found that hTERT/YBX1 may localize to the P2 region of the NRF2 promoter. Taken together, our results demonstrate that hTERT facilitates CRC proliferation and migration by upregulating NRF2 expression through the recruitment of the transcription factor YBX1 to activate the NRF2 promoter. These results provide a new theoretical basis for CRC treatment. Frontiers Media S.A. 2021-05-17 /pmc/articles/PMC8165255/ /pubmed/34079797 http://dx.doi.org/10.3389/fcell.2021.658101 Text en Copyright © 2021 Gong, Yang, Wang, Liu, Li, Hu, Chen, Huang, Luo, Wu, Liu and Xiao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Gong, Chunli
Yang, Huan
Wang, Sumin
Liu, Jiao
Li, Zhibin
Hu, Yiyang
Chen, Yang
Huang, Yu
Luo, Qiang
Wu, Yuyun
Liu, En
Xiao, Yufeng
hTERT Promotes CRC Proliferation and Migration by Recruiting YBX1 to Increase NRF2 Expression
title hTERT Promotes CRC Proliferation and Migration by Recruiting YBX1 to Increase NRF2 Expression
title_full hTERT Promotes CRC Proliferation and Migration by Recruiting YBX1 to Increase NRF2 Expression
title_fullStr hTERT Promotes CRC Proliferation and Migration by Recruiting YBX1 to Increase NRF2 Expression
title_full_unstemmed hTERT Promotes CRC Proliferation and Migration by Recruiting YBX1 to Increase NRF2 Expression
title_short hTERT Promotes CRC Proliferation and Migration by Recruiting YBX1 to Increase NRF2 Expression
title_sort htert promotes crc proliferation and migration by recruiting ybx1 to increase nrf2 expression
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165255/
https://www.ncbi.nlm.nih.gov/pubmed/34079797
http://dx.doi.org/10.3389/fcell.2021.658101
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