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ADNP Upregulation Promotes Bladder Cancer Cell Proliferation via the AKT Pathway

BACKGROUND: Activity-dependent neuroprotective protein (ADNP), which is involved in embryonic development and neurogenesis, has been proven to be upregulated in some human tumors. However, its role in bladder cancer (BC) has never been studied. OBJECTIVE: We aimed to investigate the mechanisms by wh...

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Autores principales: Zhu, Shuai, Xu, Zhenzhou, Zeng, Yong, Long, Ying, Fan, Gang, Ding, Qi, Wen, Yuheng, Cao, Jian, Dai, Tao, Han, Weiqing, Xie, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680929/
https://www.ncbi.nlm.nih.gov/pubmed/33240802
http://dx.doi.org/10.3389/fonc.2020.491129
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author Zhu, Shuai
Xu, Zhenzhou
Zeng, Yong
Long, Ying
Fan, Gang
Ding, Qi
Wen, Yuheng
Cao, Jian
Dai, Tao
Han, Weiqing
Xie, Yu
author_facet Zhu, Shuai
Xu, Zhenzhou
Zeng, Yong
Long, Ying
Fan, Gang
Ding, Qi
Wen, Yuheng
Cao, Jian
Dai, Tao
Han, Weiqing
Xie, Yu
author_sort Zhu, Shuai
collection PubMed
description BACKGROUND: Activity-dependent neuroprotective protein (ADNP), which is involved in embryonic development and neurogenesis, has been proven to be upregulated in some human tumors. However, its role in bladder cancer (BC) has never been studied. OBJECTIVE: We aimed to investigate the mechanisms by which ADNP promotes the progression of BC. METHODS: ADNP expressions in BC cell lines and paired BC and adjacent normal tissues were measured by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry. Colony formation, Cell Counting Kit-8 (CCK-8), trypan blue exclusion assay, flow cytometry, and nude mice tumorigenesis assay were performed to explore the effects of ADNP on growth of BC in vivo and in vitro. The impacts of ADNP on AKT signaling pathways were measured by Western blot. RESULTS: The expression of ADNP mRNA and protein was significantly upregulated in BC tissues compared with adjacent normal tissues. Immunohistochemical analysis of 221 BC and 51 adjacent normal tissue paraffin sections indicated that ADNP expression was significantly associated with histological classification and pathological T and N stages. Survival analysis revealed that patients with high ADNP expression have worse prognosis with respect to overall survival and progression-free disease. ADNP knockdown markedly delayed propagation of BC in vitro and the development of BC in vivo. ADNP overexpression showed the opposite effect. In addition, ADNP can markedly promote G1-S cell cycle transition in BC cells. On the molecular level, we confirmed that ADNP mediated acceleration of G1-S transition was associated with activation of the AKT pathways in BC. CONCLUSION: ADNP is overexpressed in BC and promotes BC growth partly through AKT pathways. ADNP is crucial in predicting the outcome of BC patients and may be a potential therapeutic target in BC.
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spelling pubmed-76809292020-11-24 ADNP Upregulation Promotes Bladder Cancer Cell Proliferation via the AKT Pathway Zhu, Shuai Xu, Zhenzhou Zeng, Yong Long, Ying Fan, Gang Ding, Qi Wen, Yuheng Cao, Jian Dai, Tao Han, Weiqing Xie, Yu Front Oncol Oncology BACKGROUND: Activity-dependent neuroprotective protein (ADNP), which is involved in embryonic development and neurogenesis, has been proven to be upregulated in some human tumors. However, its role in bladder cancer (BC) has never been studied. OBJECTIVE: We aimed to investigate the mechanisms by which ADNP promotes the progression of BC. METHODS: ADNP expressions in BC cell lines and paired BC and adjacent normal tissues were measured by quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry. Colony formation, Cell Counting Kit-8 (CCK-8), trypan blue exclusion assay, flow cytometry, and nude mice tumorigenesis assay were performed to explore the effects of ADNP on growth of BC in vivo and in vitro. The impacts of ADNP on AKT signaling pathways were measured by Western blot. RESULTS: The expression of ADNP mRNA and protein was significantly upregulated in BC tissues compared with adjacent normal tissues. Immunohistochemical analysis of 221 BC and 51 adjacent normal tissue paraffin sections indicated that ADNP expression was significantly associated with histological classification and pathological T and N stages. Survival analysis revealed that patients with high ADNP expression have worse prognosis with respect to overall survival and progression-free disease. ADNP knockdown markedly delayed propagation of BC in vitro and the development of BC in vivo. ADNP overexpression showed the opposite effect. In addition, ADNP can markedly promote G1-S cell cycle transition in BC cells. On the molecular level, we confirmed that ADNP mediated acceleration of G1-S transition was associated with activation of the AKT pathways in BC. CONCLUSION: ADNP is overexpressed in BC and promotes BC growth partly through AKT pathways. ADNP is crucial in predicting the outcome of BC patients and may be a potential therapeutic target in BC. Frontiers Media S.A. 2020-11-09 /pmc/articles/PMC7680929/ /pubmed/33240802 http://dx.doi.org/10.3389/fonc.2020.491129 Text en Copyright © 2020 Zhu, Xu, Zeng, Long, Fan, Ding, Wen, Cao, Dai, Han and Xie http://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 Oncology
Zhu, Shuai
Xu, Zhenzhou
Zeng, Yong
Long, Ying
Fan, Gang
Ding, Qi
Wen, Yuheng
Cao, Jian
Dai, Tao
Han, Weiqing
Xie, Yu
ADNP Upregulation Promotes Bladder Cancer Cell Proliferation via the AKT Pathway
title ADNP Upregulation Promotes Bladder Cancer Cell Proliferation via the AKT Pathway
title_full ADNP Upregulation Promotes Bladder Cancer Cell Proliferation via the AKT Pathway
title_fullStr ADNP Upregulation Promotes Bladder Cancer Cell Proliferation via the AKT Pathway
title_full_unstemmed ADNP Upregulation Promotes Bladder Cancer Cell Proliferation via the AKT Pathway
title_short ADNP Upregulation Promotes Bladder Cancer Cell Proliferation via the AKT Pathway
title_sort adnp upregulation promotes bladder cancer cell proliferation via the akt pathway
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680929/
https://www.ncbi.nlm.nih.gov/pubmed/33240802
http://dx.doi.org/10.3389/fonc.2020.491129
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