TCRP1 transcriptionally regulated by c-Myc confers cancer chemoresistance in tongue and lung cancer

Abstract Previously, we cloned a new gene termed ‘tongue cancer resistance-associated protein 1’ (TCRP1), which modulates tumorigenesis, enhances cisplatin (cDDP) resistance in cancers, and may be a potential target for reversing drug resistance. However, the mechanisms for regulating TCRP1 expressi...

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Autores principales: Xiaoting Jia, Zhijie Zhang, Kai Luo, Guopei Zheng, Minying Lu, Ying Song, Hao Liu, Huisi Qiu, Zhimin He
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/9d6d93dabe994a2ba343e17400ab6d6a
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spelling oai:doaj.org-article:9d6d93dabe994a2ba343e17400ab6d6a2021-12-02T16:07:05ZTCRP1 transcriptionally regulated by c-Myc confers cancer chemoresistance in tongue and lung cancer10.1038/s41598-017-03763-02045-2322https://doaj.org/article/9d6d93dabe994a2ba343e17400ab6d6a2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03763-0https://doaj.org/toc/2045-2322Abstract Previously, we cloned a new gene termed ‘tongue cancer resistance-associated protein 1’ (TCRP1), which modulates tumorigenesis, enhances cisplatin (cDDP) resistance in cancers, and may be a potential target for reversing drug resistance. However, the mechanisms for regulating TCRP1 expression remain unclear. Herein, we combined bioinformatics analysis with luciferase reporter assay and ChIP assay to determine that c-Myc could directly bind to TCRP1 promoter to upregulate its expression. TCRP1 upregulation in multidrug resistant tongue cancer cells (Tca8113/PYM) and cisplatin-resistant A549 lung cancer cells (A549/DDP) was accompanied by c-Myc upregulation, compared to respective parental cells. In tongue and lung cancer cells, siRNA-mediated knockdown of c-Myc led to decrease TCRP1 expression, whereas overexpression c-Myc did the opposite. Moreover, TCRP1 knockdown attenuated chemoresistance resulting from c-Myc overexpression, but TCRP1 overexpression impaired the effect of c-Myc knockdown on chemosensitivity. Additionally, in both human tongue and lung cancer tissues, c-Myc protein expression positively correlated with TCRP1 protein expression and these protein levels were associated with worse prognosis for patients. Combined, these findings suggest that c-Myc could transcriptionally regulate TCRP1 in cell lines and clinical samples and identified the c-Myc-TCRP1 axis as a negative biomarker of prognosis in tongue and lung cancers.Xiaoting JiaZhijie ZhangKai LuoGuopei ZhengMinying LuYing SongHao LiuHuisi QiuZhimin HeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Xiaoting Jia
Zhijie Zhang
Kai Luo
Guopei Zheng
Minying Lu
Ying Song
Hao Liu
Huisi Qiu
Zhimin He
TCRP1 transcriptionally regulated by c-Myc confers cancer chemoresistance in tongue and lung cancer
description Abstract Previously, we cloned a new gene termed ‘tongue cancer resistance-associated protein 1’ (TCRP1), which modulates tumorigenesis, enhances cisplatin (cDDP) resistance in cancers, and may be a potential target for reversing drug resistance. However, the mechanisms for regulating TCRP1 expression remain unclear. Herein, we combined bioinformatics analysis with luciferase reporter assay and ChIP assay to determine that c-Myc could directly bind to TCRP1 promoter to upregulate its expression. TCRP1 upregulation in multidrug resistant tongue cancer cells (Tca8113/PYM) and cisplatin-resistant A549 lung cancer cells (A549/DDP) was accompanied by c-Myc upregulation, compared to respective parental cells. In tongue and lung cancer cells, siRNA-mediated knockdown of c-Myc led to decrease TCRP1 expression, whereas overexpression c-Myc did the opposite. Moreover, TCRP1 knockdown attenuated chemoresistance resulting from c-Myc overexpression, but TCRP1 overexpression impaired the effect of c-Myc knockdown on chemosensitivity. Additionally, in both human tongue and lung cancer tissues, c-Myc protein expression positively correlated with TCRP1 protein expression and these protein levels were associated with worse prognosis for patients. Combined, these findings suggest that c-Myc could transcriptionally regulate TCRP1 in cell lines and clinical samples and identified the c-Myc-TCRP1 axis as a negative biomarker of prognosis in tongue and lung cancers.
format article
author Xiaoting Jia
Zhijie Zhang
Kai Luo
Guopei Zheng
Minying Lu
Ying Song
Hao Liu
Huisi Qiu
Zhimin He
author_facet Xiaoting Jia
Zhijie Zhang
Kai Luo
Guopei Zheng
Minying Lu
Ying Song
Hao Liu
Huisi Qiu
Zhimin He
author_sort Xiaoting Jia
title TCRP1 transcriptionally regulated by c-Myc confers cancer chemoresistance in tongue and lung cancer
title_short TCRP1 transcriptionally regulated by c-Myc confers cancer chemoresistance in tongue and lung cancer
title_full TCRP1 transcriptionally regulated by c-Myc confers cancer chemoresistance in tongue and lung cancer
title_fullStr TCRP1 transcriptionally regulated by c-Myc confers cancer chemoresistance in tongue and lung cancer
title_full_unstemmed TCRP1 transcriptionally regulated by c-Myc confers cancer chemoresistance in tongue and lung cancer
title_sort tcrp1 transcriptionally regulated by c-myc confers cancer chemoresistance in tongue and lung cancer
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/9d6d93dabe994a2ba343e17400ab6d6a
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