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TRIM44 promotes BRCA1 functions in HR repair to induce Cisplatin Chemoresistance in Lung Adenocarcinoma by Deubiquitinating FLNA
Tripartite motif-containing 44 (TRIM44) has recently been implicated in various pathological processes in numerous cancers, including lung adenocarcinoma (LUAD); however, its functional roles in chemoresistance are poorly understood. Herein, TRIM44 knockdown sensitized LUAD cells to cisplatin and en...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Ivyspring International Publisher
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9066100/ https://www.ncbi.nlm.nih.gov/pubmed/35541909 http://dx.doi.org/10.7150/ijbs.71283 |
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author | Zhang, Shuai Cao, Mengru Yan, Shi Liu, Yuechao Fan, Weina Cui, Yimeng Tian, Fanglin Gu, Ruixue Cui, Yaowen Zhan, Yuning Sun, Yuanyuan Xing, Ying Cai, Li Song, Yang |
author_facet | Zhang, Shuai Cao, Mengru Yan, Shi Liu, Yuechao Fan, Weina Cui, Yimeng Tian, Fanglin Gu, Ruixue Cui, Yaowen Zhan, Yuning Sun, Yuanyuan Xing, Ying Cai, Li Song, Yang |
author_sort | Zhang, Shuai |
collection | PubMed |
description | Tripartite motif-containing 44 (TRIM44) has recently been implicated in various pathological processes in numerous cancers, including lung adenocarcinoma (LUAD); however, its functional roles in chemoresistance are poorly understood. Herein, TRIM44 knockdown sensitized LUAD cells to cisplatin and enhanced cisplatin-induced apoptosis. Microarray analysis indicated that the “Role of BRCA1 in DNA damage” and the BRCA1 gene expression were positively regulated by TRIM44, which was further verified by immunofluorescence, qRT-PCR, and Western blotting. BRCA1 depletion effectively abolished TRIM44-modulated cisplatin resistance and regulation of homologous recombination (HR) repair. Interestingly, TRIM44 interacted with FLNA, an upstream regulator of BRCA1 as specified by STRING V 11.5, and facilitated its stability and deubiquitination. FLNA was also found to be required for the functions of TRIM44 in drug resistance. Using animal models, overexpression of TRIM44 was shown to confer resistance to cisplatin in a BRCA1- and FLNA-dependent manner. TRIM44 expression levels in tissues from cisplatin-resistant LUAD patients were significantly higher than those in tissues from cisplatin-sensitive LUAD patients. Collectively, our study results demonstrate that the TRIM44/FLNA/BRCA1 axis is involved in cisplatin chemoresistance, providing potential therapeutic targets for LUAD patients with cisplatin resistance. |
format | Online Article Text |
id | pubmed-9066100 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-90661002022-05-09 TRIM44 promotes BRCA1 functions in HR repair to induce Cisplatin Chemoresistance in Lung Adenocarcinoma by Deubiquitinating FLNA Zhang, Shuai Cao, Mengru Yan, Shi Liu, Yuechao Fan, Weina Cui, Yimeng Tian, Fanglin Gu, Ruixue Cui, Yaowen Zhan, Yuning Sun, Yuanyuan Xing, Ying Cai, Li Song, Yang Int J Biol Sci Research Paper Tripartite motif-containing 44 (TRIM44) has recently been implicated in various pathological processes in numerous cancers, including lung adenocarcinoma (LUAD); however, its functional roles in chemoresistance are poorly understood. Herein, TRIM44 knockdown sensitized LUAD cells to cisplatin and enhanced cisplatin-induced apoptosis. Microarray analysis indicated that the “Role of BRCA1 in DNA damage” and the BRCA1 gene expression were positively regulated by TRIM44, which was further verified by immunofluorescence, qRT-PCR, and Western blotting. BRCA1 depletion effectively abolished TRIM44-modulated cisplatin resistance and regulation of homologous recombination (HR) repair. Interestingly, TRIM44 interacted with FLNA, an upstream regulator of BRCA1 as specified by STRING V 11.5, and facilitated its stability and deubiquitination. FLNA was also found to be required for the functions of TRIM44 in drug resistance. Using animal models, overexpression of TRIM44 was shown to confer resistance to cisplatin in a BRCA1- and FLNA-dependent manner. TRIM44 expression levels in tissues from cisplatin-resistant LUAD patients were significantly higher than those in tissues from cisplatin-sensitive LUAD patients. Collectively, our study results demonstrate that the TRIM44/FLNA/BRCA1 axis is involved in cisplatin chemoresistance, providing potential therapeutic targets for LUAD patients with cisplatin resistance. Ivyspring International Publisher 2022-04-18 /pmc/articles/PMC9066100/ /pubmed/35541909 http://dx.doi.org/10.7150/ijbs.71283 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Zhang, Shuai Cao, Mengru Yan, Shi Liu, Yuechao Fan, Weina Cui, Yimeng Tian, Fanglin Gu, Ruixue Cui, Yaowen Zhan, Yuning Sun, Yuanyuan Xing, Ying Cai, Li Song, Yang TRIM44 promotes BRCA1 functions in HR repair to induce Cisplatin Chemoresistance in Lung Adenocarcinoma by Deubiquitinating FLNA |
title | TRIM44 promotes BRCA1 functions in HR repair to induce Cisplatin Chemoresistance in Lung Adenocarcinoma by Deubiquitinating FLNA |
title_full | TRIM44 promotes BRCA1 functions in HR repair to induce Cisplatin Chemoresistance in Lung Adenocarcinoma by Deubiquitinating FLNA |
title_fullStr | TRIM44 promotes BRCA1 functions in HR repair to induce Cisplatin Chemoresistance in Lung Adenocarcinoma by Deubiquitinating FLNA |
title_full_unstemmed | TRIM44 promotes BRCA1 functions in HR repair to induce Cisplatin Chemoresistance in Lung Adenocarcinoma by Deubiquitinating FLNA |
title_short | TRIM44 promotes BRCA1 functions in HR repair to induce Cisplatin Chemoresistance in Lung Adenocarcinoma by Deubiquitinating FLNA |
title_sort | trim44 promotes brca1 functions in hr repair to induce cisplatin chemoresistance in lung adenocarcinoma by deubiquitinating flna |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9066100/ https://www.ncbi.nlm.nih.gov/pubmed/35541909 http://dx.doi.org/10.7150/ijbs.71283 |
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