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LAMP3 plays an oncogenic role in osteosarcoma cells partially by inhibiting TP53

BACKGROUND: Osteosarcoma (OS) is a common malignant tumor that predominantly occurs in adolescents. Its most common metastasis is to the lungs. As shown in our earlier study, lysosome-associated membrane glycoprotein 3 (LAMP3) is highly upregulated in metastatic OS. However, its role in the regulati...

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Autores principales: Liu, Shaoxian, Yue, Junyi, Du, Wei, Han, Jian, Zhang, Weidong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042264/
https://www.ncbi.nlm.nih.gov/pubmed/30008754
http://dx.doi.org/10.1186/s11658-018-0099-8
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author Liu, Shaoxian
Yue, Junyi
Du, Wei
Han, Jian
Zhang, Weidong
author_facet Liu, Shaoxian
Yue, Junyi
Du, Wei
Han, Jian
Zhang, Weidong
author_sort Liu, Shaoxian
collection PubMed
description BACKGROUND: Osteosarcoma (OS) is a common malignant tumor that predominantly occurs in adolescents. Its most common metastasis is to the lungs. As shown in our earlier study, lysosome-associated membrane glycoprotein 3 (LAMP3) is highly upregulated in metastatic OS. However, its role in the regulation of OS cell viability and apoptosis remains unknown. METHODS: We knocked down and overexpressed LAMP3 in OS cells and assessed the cell viability and apoptosis. Then, we investigated the expression of apoptosis-associated genes to identify the downstream gene(s) of LAMP3. RESULTS: Knockdown of LAMP3 significantly inhibited OS cell viability and promoted apoptosis. TP53, which is involved in the apoptosis pathway, was found to be highly upregulated after knockdown of LAMP3. Overexpression of LAMP3 significantly increased cell viability and abrogated apoptosis. Importantly, subsequent knockdown of TP53 partially suppressed the increased OS cell apoptosis induced by the inhibition of LAMP3, suggesting that TP53 is a key functional downstream gene of LAMP3. CONCLUSIONS: Our findings suggest that LAMP3 promotes OS cell viability and survival by regulating TP53 expression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s11658-018-0099-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-60422642018-07-13 LAMP3 plays an oncogenic role in osteosarcoma cells partially by inhibiting TP53 Liu, Shaoxian Yue, Junyi Du, Wei Han, Jian Zhang, Weidong Cell Mol Biol Lett Short Report BACKGROUND: Osteosarcoma (OS) is a common malignant tumor that predominantly occurs in adolescents. Its most common metastasis is to the lungs. As shown in our earlier study, lysosome-associated membrane glycoprotein 3 (LAMP3) is highly upregulated in metastatic OS. However, its role in the regulation of OS cell viability and apoptosis remains unknown. METHODS: We knocked down and overexpressed LAMP3 in OS cells and assessed the cell viability and apoptosis. Then, we investigated the expression of apoptosis-associated genes to identify the downstream gene(s) of LAMP3. RESULTS: Knockdown of LAMP3 significantly inhibited OS cell viability and promoted apoptosis. TP53, which is involved in the apoptosis pathway, was found to be highly upregulated after knockdown of LAMP3. Overexpression of LAMP3 significantly increased cell viability and abrogated apoptosis. Importantly, subsequent knockdown of TP53 partially suppressed the increased OS cell apoptosis induced by the inhibition of LAMP3, suggesting that TP53 is a key functional downstream gene of LAMP3. CONCLUSIONS: Our findings suggest that LAMP3 promotes OS cell viability and survival by regulating TP53 expression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s11658-018-0099-8) contains supplementary material, which is available to authorized users. BioMed Central 2018-07-11 /pmc/articles/PMC6042264/ /pubmed/30008754 http://dx.doi.org/10.1186/s11658-018-0099-8 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Short Report
Liu, Shaoxian
Yue, Junyi
Du, Wei
Han, Jian
Zhang, Weidong
LAMP3 plays an oncogenic role in osteosarcoma cells partially by inhibiting TP53
title LAMP3 plays an oncogenic role in osteosarcoma cells partially by inhibiting TP53
title_full LAMP3 plays an oncogenic role in osteosarcoma cells partially by inhibiting TP53
title_fullStr LAMP3 plays an oncogenic role in osteosarcoma cells partially by inhibiting TP53
title_full_unstemmed LAMP3 plays an oncogenic role in osteosarcoma cells partially by inhibiting TP53
title_short LAMP3 plays an oncogenic role in osteosarcoma cells partially by inhibiting TP53
title_sort lamp3 plays an oncogenic role in osteosarcoma cells partially by inhibiting tp53
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042264/
https://www.ncbi.nlm.nih.gov/pubmed/30008754
http://dx.doi.org/10.1186/s11658-018-0099-8
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