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lncRNA MALAT1 Promotes EMT Process and Cisplatin Resistance of Oral Squamous Cell Carcinoma via PI3K/AKT/m-TOR Signal Pathway

BACKGROUND: Cisplatin (DDP) is the first-line chemotherapy agent for the treatment of oral squamous cell carcinoma (OSCC). The emergence of DDP resistance leads to diminished drug efficacy and survival benefit. lncRNA MALAT1 has been considered as one of the most important factors in OSCC. It has al...

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Autores principales: Wang, Ran, Lu, Xinxing, Yu, Riyue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231756/
https://www.ncbi.nlm.nih.gov/pubmed/32494159
http://dx.doi.org/10.2147/OTT.S251518
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author Wang, Ran
Lu, Xinxing
Yu, Riyue
author_facet Wang, Ran
Lu, Xinxing
Yu, Riyue
author_sort Wang, Ran
collection PubMed
description BACKGROUND: Cisplatin (DDP) is the first-line chemotherapy agent for the treatment of oral squamous cell carcinoma (OSCC). The emergence of DDP resistance leads to diminished drug efficacy and survival benefit. lncRNA MALAT1 has been considered as one of the most important factors in OSCC. It has also been reported to enhance chemo-resistance in other kinds of carcinomas. However, little is known about the role of lncRNA MALAT1 in DDP resistance of OSCC. MATERIALS AND METHODS: Two kinds of human DDP-resistant cell lines (CAL-27R and SCC-9R) were developed from cisplatin-naïve cell lines (CAL-27 and SCC-9, respectively) as in vitro cell models. Cell transfection was performed to overexpress or knockdown MALAT1 in these cells. Mouse xenograft models were also established. The following measurements were performed: cell proliferation, colony formation, wound healing, transwell, and TUNEL assays, as well as Western blot and immunofluorescence staining. RESULTS: DDP-resistant cells showed higher expression level of MALAT1 compared to cisplatin-naïve cells. The overexpression of MALAT1 in cisplatin-naïve cells enhanced DDP resistance and suppressed apoptosis in OSCC cells. However, the knockdown of MALAT1 in DDP-resistance cells induced apoptotic cell death and restored the sensitivity to DDP. Further analyses suggested that MALAT1 might promote DDP resistance via regulating P-glycoprotein expression, epithelial–mesenchymal transition process, and the activation of PI3K/AKT/m-TOR signaling pathway. CONCLUSION: MALAT1 might be a potential therapeutic target for the treatment of DDP-resistant OSCC.
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spelling pubmed-72317562020-06-02 lncRNA MALAT1 Promotes EMT Process and Cisplatin Resistance of Oral Squamous Cell Carcinoma via PI3K/AKT/m-TOR Signal Pathway Wang, Ran Lu, Xinxing Yu, Riyue Onco Targets Ther Original Research BACKGROUND: Cisplatin (DDP) is the first-line chemotherapy agent for the treatment of oral squamous cell carcinoma (OSCC). The emergence of DDP resistance leads to diminished drug efficacy and survival benefit. lncRNA MALAT1 has been considered as one of the most important factors in OSCC. It has also been reported to enhance chemo-resistance in other kinds of carcinomas. However, little is known about the role of lncRNA MALAT1 in DDP resistance of OSCC. MATERIALS AND METHODS: Two kinds of human DDP-resistant cell lines (CAL-27R and SCC-9R) were developed from cisplatin-naïve cell lines (CAL-27 and SCC-9, respectively) as in vitro cell models. Cell transfection was performed to overexpress or knockdown MALAT1 in these cells. Mouse xenograft models were also established. The following measurements were performed: cell proliferation, colony formation, wound healing, transwell, and TUNEL assays, as well as Western blot and immunofluorescence staining. RESULTS: DDP-resistant cells showed higher expression level of MALAT1 compared to cisplatin-naïve cells. The overexpression of MALAT1 in cisplatin-naïve cells enhanced DDP resistance and suppressed apoptosis in OSCC cells. However, the knockdown of MALAT1 in DDP-resistance cells induced apoptotic cell death and restored the sensitivity to DDP. Further analyses suggested that MALAT1 might promote DDP resistance via regulating P-glycoprotein expression, epithelial–mesenchymal transition process, and the activation of PI3K/AKT/m-TOR signaling pathway. CONCLUSION: MALAT1 might be a potential therapeutic target for the treatment of DDP-resistant OSCC. Dove 2020-05-12 /pmc/articles/PMC7231756/ /pubmed/32494159 http://dx.doi.org/10.2147/OTT.S251518 Text en © 2020 Wang et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Wang, Ran
Lu, Xinxing
Yu, Riyue
lncRNA MALAT1 Promotes EMT Process and Cisplatin Resistance of Oral Squamous Cell Carcinoma via PI3K/AKT/m-TOR Signal Pathway
title lncRNA MALAT1 Promotes EMT Process and Cisplatin Resistance of Oral Squamous Cell Carcinoma via PI3K/AKT/m-TOR Signal Pathway
title_full lncRNA MALAT1 Promotes EMT Process and Cisplatin Resistance of Oral Squamous Cell Carcinoma via PI3K/AKT/m-TOR Signal Pathway
title_fullStr lncRNA MALAT1 Promotes EMT Process and Cisplatin Resistance of Oral Squamous Cell Carcinoma via PI3K/AKT/m-TOR Signal Pathway
title_full_unstemmed lncRNA MALAT1 Promotes EMT Process and Cisplatin Resistance of Oral Squamous Cell Carcinoma via PI3K/AKT/m-TOR Signal Pathway
title_short lncRNA MALAT1 Promotes EMT Process and Cisplatin Resistance of Oral Squamous Cell Carcinoma via PI3K/AKT/m-TOR Signal Pathway
title_sort lncrna malat1 promotes emt process and cisplatin resistance of oral squamous cell carcinoma via pi3k/akt/m-tor signal pathway
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231756/
https://www.ncbi.nlm.nih.gov/pubmed/32494159
http://dx.doi.org/10.2147/OTT.S251518
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