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TP53TG1 enhances cisplatin sensitivity of non-small cell lung cancer cells through regulating miR-18a/PTEN axis

BACKGROUND: The acquisition of drug resistance has been considered as a main obstacle for cancer chemotherapy. Tumor protein 53 target gene 1 (TP53TG1), a p53-induced lncRNA, plays a vital role in the progression of human cancers. However, little is known about the detailed function and molecular me...

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Autores principales: Xiao, Huijuan, Liu, Yihe, Liang, Pan, Wang, Bo, Tan, Hongna, Zhang, Yonggao, Gao, Xianzheng, Gao, Jianbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863826/
https://www.ncbi.nlm.nih.gov/pubmed/29588850
http://dx.doi.org/10.1186/s13578-018-0221-7
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author Xiao, Huijuan
Liu, Yihe
Liang, Pan
Wang, Bo
Tan, Hongna
Zhang, Yonggao
Gao, Xianzheng
Gao, Jianbo
author_facet Xiao, Huijuan
Liu, Yihe
Liang, Pan
Wang, Bo
Tan, Hongna
Zhang, Yonggao
Gao, Xianzheng
Gao, Jianbo
author_sort Xiao, Huijuan
collection PubMed
description BACKGROUND: The acquisition of drug resistance has been considered as a main obstacle for cancer chemotherapy. Tumor protein 53 target gene 1 (TP53TG1), a p53-induced lncRNA, plays a vital role in the progression of human cancers. However, little is known about the detailed function and molecular mechanism of TP53TG1 in cisplatin resistance of NSCLC. METHODS: qRT-PCR analysis was used to detect the expression of TP53TG1, miR-18a and PTEN mRNA in NSCLC tissues and cells. Western blot analysis was performed to determine the protein level of PTEN and cleaved caspase-3. Cell viability and IC50 value were measured by MTT assay. Cell apoptosis was confirmed by flow cytometry assay. Subcellular fractionation assay was used to identify the subcellular location of TP53TG1. Dual-luciferase reporter assay, RNA pull down assay and RNA immunoprecipitation assay were carried out to verify the interaction between TP53TG1 and miR-18a. Xenografts in nude mice were established to verify the effect of TP53TG1 on cisplatin sensitivity of NSCLC cells in vivo. RESULTS: TP53TG1 level was downregulated in NSCLC tissues and cell lines. Upregulated TP53TG1 enhanced cisplatin sensitivity and apoptosis of A549/DDP cells, while TP53TG1 depletion inhibited cisplatin sensitivity and apoptosis of A549 cells. TP53TG1 suppressed miR-18a expression in A549 cells. Moreover, TP53TG1-mediated enhancement effect on cisplatin sensitivity was abated following the restoration of miR-18a expression in A549/DDP cells, while si-TP53TG1-induced decrease of cisplatin sensitivity and apoptosis was counteracted by miR-18a inhibitor in A549 cells. Furthermore, TP53TG1 promoted PTEN expression via inhibiting miR-18a. Finally, TP53TG1 sensitized NSCLC cells to cisplatin in vivo. CONCLUSION: TP53TG1 increased the sensitivity of NSCLC cells to cisplatin by modulating miR-18a/PTEN axis, elucidating a novel approach to boost the effectiveness of chemotherapy for NSCLC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13578-018-0221-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-58638262018-03-27 TP53TG1 enhances cisplatin sensitivity of non-small cell lung cancer cells through regulating miR-18a/PTEN axis Xiao, Huijuan Liu, Yihe Liang, Pan Wang, Bo Tan, Hongna Zhang, Yonggao Gao, Xianzheng Gao, Jianbo Cell Biosci Research BACKGROUND: The acquisition of drug resistance has been considered as a main obstacle for cancer chemotherapy. Tumor protein 53 target gene 1 (TP53TG1), a p53-induced lncRNA, plays a vital role in the progression of human cancers. However, little is known about the detailed function and molecular mechanism of TP53TG1 in cisplatin resistance of NSCLC. METHODS: qRT-PCR analysis was used to detect the expression of TP53TG1, miR-18a and PTEN mRNA in NSCLC tissues and cells. Western blot analysis was performed to determine the protein level of PTEN and cleaved caspase-3. Cell viability and IC50 value were measured by MTT assay. Cell apoptosis was confirmed by flow cytometry assay. Subcellular fractionation assay was used to identify the subcellular location of TP53TG1. Dual-luciferase reporter assay, RNA pull down assay and RNA immunoprecipitation assay were carried out to verify the interaction between TP53TG1 and miR-18a. Xenografts in nude mice were established to verify the effect of TP53TG1 on cisplatin sensitivity of NSCLC cells in vivo. RESULTS: TP53TG1 level was downregulated in NSCLC tissues and cell lines. Upregulated TP53TG1 enhanced cisplatin sensitivity and apoptosis of A549/DDP cells, while TP53TG1 depletion inhibited cisplatin sensitivity and apoptosis of A549 cells. TP53TG1 suppressed miR-18a expression in A549 cells. Moreover, TP53TG1-mediated enhancement effect on cisplatin sensitivity was abated following the restoration of miR-18a expression in A549/DDP cells, while si-TP53TG1-induced decrease of cisplatin sensitivity and apoptosis was counteracted by miR-18a inhibitor in A549 cells. Furthermore, TP53TG1 promoted PTEN expression via inhibiting miR-18a. Finally, TP53TG1 sensitized NSCLC cells to cisplatin in vivo. CONCLUSION: TP53TG1 increased the sensitivity of NSCLC cells to cisplatin by modulating miR-18a/PTEN axis, elucidating a novel approach to boost the effectiveness of chemotherapy for NSCLC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13578-018-0221-7) contains supplementary material, which is available to authorized users. BioMed Central 2018-03-22 /pmc/articles/PMC5863826/ /pubmed/29588850 http://dx.doi.org/10.1186/s13578-018-0221-7 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 Research
Xiao, Huijuan
Liu, Yihe
Liang, Pan
Wang, Bo
Tan, Hongna
Zhang, Yonggao
Gao, Xianzheng
Gao, Jianbo
TP53TG1 enhances cisplatin sensitivity of non-small cell lung cancer cells through regulating miR-18a/PTEN axis
title TP53TG1 enhances cisplatin sensitivity of non-small cell lung cancer cells through regulating miR-18a/PTEN axis
title_full TP53TG1 enhances cisplatin sensitivity of non-small cell lung cancer cells through regulating miR-18a/PTEN axis
title_fullStr TP53TG1 enhances cisplatin sensitivity of non-small cell lung cancer cells through regulating miR-18a/PTEN axis
title_full_unstemmed TP53TG1 enhances cisplatin sensitivity of non-small cell lung cancer cells through regulating miR-18a/PTEN axis
title_short TP53TG1 enhances cisplatin sensitivity of non-small cell lung cancer cells through regulating miR-18a/PTEN axis
title_sort tp53tg1 enhances cisplatin sensitivity of non-small cell lung cancer cells through regulating mir-18a/pten axis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863826/
https://www.ncbi.nlm.nih.gov/pubmed/29588850
http://dx.doi.org/10.1186/s13578-018-0221-7
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