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LNC00115 Mediates Cisplatin Resistance by Regulating the miR-7/ERK Signalling Pathway in Ovarian Cancer

BACKGROUND: Ovarian cancer has one of the highest mortality rates among all gynaecological malignancies, and increasing evidence suggests that lncRNAs are widely involved in the development of ovarian tumours. This study aimed to investigate the mechanism of the LNC00115/miR-7/ERK axis in the cispla...

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Autores principales: Jiang, Xinyan, Cheng, Yan, He, Yanan, Cong, Shanshan, Sun, Liyuan, Wu, Di, Wu, Han, Zhang, Guangmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123956/
https://www.ncbi.nlm.nih.gov/pubmed/34007214
http://dx.doi.org/10.2147/CMAR.S295097
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author Jiang, Xinyan
Cheng, Yan
He, Yanan
Cong, Shanshan
Sun, Liyuan
Wu, Di
Wu, Han
Zhang, Guangmei
author_facet Jiang, Xinyan
Cheng, Yan
He, Yanan
Cong, Shanshan
Sun, Liyuan
Wu, Di
Wu, Han
Zhang, Guangmei
author_sort Jiang, Xinyan
collection PubMed
description BACKGROUND: Ovarian cancer has one of the highest mortality rates among all gynaecological malignancies, and increasing evidence suggests that lncRNAs are widely involved in the development of ovarian tumours. This study aimed to investigate the mechanism of the LNC00115/miR-7/ERK axis in the cisplatin resistance of ovarian cancer cells. METHODS: The expression of miR-7 and LNC00115 in ovarian cancer cell lines and tissues was detected by qRT-PCR. The ovarian cancer cell lines were constructed by overexpressing or knocking down the expression of LNC00115 or miR-7. CCK-8, transwell invasion, Western blot, immunohistochemistry, and luciferase reporter assays were carried out to identify the targets of LNC00115 and explore its roles and mechanisms in ovarian cancer. A nude mouse model was established, and the expression of LNC00115, miR-7 and ERK was detected. The changes in the tumours and body weights of the nude mice were measured. RESULTS: LNC00115 was upregulated in ovarian cancer tissues and cisplatin-resistant ovarian cancer cells. Moreover, LNC00115 promoted the cisplatin resistance, invasion and migration of ovarian cancer cells. LNC00115 was shown to directly target miR-7, and miR-7 was downregulated in ovarian cancer tissues and cisplatin-resistant ovarian cancer cells. miR-7 inhibited the cisplatin resistance, invasion and migration of ovarian cancer cells and directly targeted ERK. ERK was overexpressed in cisplatin-resistant ovarian cancer cells and ovarian cancer tissues. In animal experiments, overexpression of LNC00115 enhanced the cisplatin resistance of ovarian cancer cells, while miR-7 had the opposite effect. Mechanistically, LNC00115 sponged miR-7 to increase the expression of ERK, which in turn enhanced the cisplatin resistance of ovarian cancer. CONCLUSION: Our data clarify the mechanism by which the LNC00115/miR-7/ERK axis promotes cisplatin resistance and provide a new clinical strategy for combating cisplatin resistance in ovarian cancer.
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spelling pubmed-81239562021-05-17 LNC00115 Mediates Cisplatin Resistance by Regulating the miR-7/ERK Signalling Pathway in Ovarian Cancer Jiang, Xinyan Cheng, Yan He, Yanan Cong, Shanshan Sun, Liyuan Wu, Di Wu, Han Zhang, Guangmei Cancer Manag Res Original Research BACKGROUND: Ovarian cancer has one of the highest mortality rates among all gynaecological malignancies, and increasing evidence suggests that lncRNAs are widely involved in the development of ovarian tumours. This study aimed to investigate the mechanism of the LNC00115/miR-7/ERK axis in the cisplatin resistance of ovarian cancer cells. METHODS: The expression of miR-7 and LNC00115 in ovarian cancer cell lines and tissues was detected by qRT-PCR. The ovarian cancer cell lines were constructed by overexpressing or knocking down the expression of LNC00115 or miR-7. CCK-8, transwell invasion, Western blot, immunohistochemistry, and luciferase reporter assays were carried out to identify the targets of LNC00115 and explore its roles and mechanisms in ovarian cancer. A nude mouse model was established, and the expression of LNC00115, miR-7 and ERK was detected. The changes in the tumours and body weights of the nude mice were measured. RESULTS: LNC00115 was upregulated in ovarian cancer tissues and cisplatin-resistant ovarian cancer cells. Moreover, LNC00115 promoted the cisplatin resistance, invasion and migration of ovarian cancer cells. LNC00115 was shown to directly target miR-7, and miR-7 was downregulated in ovarian cancer tissues and cisplatin-resistant ovarian cancer cells. miR-7 inhibited the cisplatin resistance, invasion and migration of ovarian cancer cells and directly targeted ERK. ERK was overexpressed in cisplatin-resistant ovarian cancer cells and ovarian cancer tissues. In animal experiments, overexpression of LNC00115 enhanced the cisplatin resistance of ovarian cancer cells, while miR-7 had the opposite effect. Mechanistically, LNC00115 sponged miR-7 to increase the expression of ERK, which in turn enhanced the cisplatin resistance of ovarian cancer. CONCLUSION: Our data clarify the mechanism by which the LNC00115/miR-7/ERK axis promotes cisplatin resistance and provide a new clinical strategy for combating cisplatin resistance in ovarian cancer. Dove 2021-05-11 /pmc/articles/PMC8123956/ /pubmed/34007214 http://dx.doi.org/10.2147/CMAR.S295097 Text en © 2021 Jiang et al. https://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/ (https://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
Jiang, Xinyan
Cheng, Yan
He, Yanan
Cong, Shanshan
Sun, Liyuan
Wu, Di
Wu, Han
Zhang, Guangmei
LNC00115 Mediates Cisplatin Resistance by Regulating the miR-7/ERK Signalling Pathway in Ovarian Cancer
title LNC00115 Mediates Cisplatin Resistance by Regulating the miR-7/ERK Signalling Pathway in Ovarian Cancer
title_full LNC00115 Mediates Cisplatin Resistance by Regulating the miR-7/ERK Signalling Pathway in Ovarian Cancer
title_fullStr LNC00115 Mediates Cisplatin Resistance by Regulating the miR-7/ERK Signalling Pathway in Ovarian Cancer
title_full_unstemmed LNC00115 Mediates Cisplatin Resistance by Regulating the miR-7/ERK Signalling Pathway in Ovarian Cancer
title_short LNC00115 Mediates Cisplatin Resistance by Regulating the miR-7/ERK Signalling Pathway in Ovarian Cancer
title_sort lnc00115 mediates cisplatin resistance by regulating the mir-7/erk signalling pathway in ovarian cancer
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123956/
https://www.ncbi.nlm.nih.gov/pubmed/34007214
http://dx.doi.org/10.2147/CMAR.S295097
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