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Mxi1 participates in the progression of lung cancer via the microRNA-300/KLF9/GADD34 Axis
The purpose of the current study was to define the role of MAX interactor 1 (Mxi1) in the pathogenesis of lung cancer and its underlying molecular mechanism. Bioinformatics analysis was performed to identify important regulatory pathway related to lung cancer. Dual luciferase reporter and ChIP assay...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9061846/ https://www.ncbi.nlm.nih.gov/pubmed/35501353 http://dx.doi.org/10.1038/s41419-022-04778-w |
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author | Lei, Yujie Huang, Yunchao Lin, Jianbin Sun, Shihui Che, Keda Shen, Junting Liao, Jun Chen, Yangming Chen, Kai Lin, Zhaoxian Lin, Xing |
author_facet | Lei, Yujie Huang, Yunchao Lin, Jianbin Sun, Shihui Che, Keda Shen, Junting Liao, Jun Chen, Yangming Chen, Kai Lin, Zhaoxian Lin, Xing |
author_sort | Lei, Yujie |
collection | PubMed |
description | The purpose of the current study was to define the role of MAX interactor 1 (Mxi1) in the pathogenesis of lung cancer and its underlying molecular mechanism. Bioinformatics analysis was performed to identify important regulatory pathway related to lung cancer. Dual luciferase reporter and ChIP assays were adopted to validate the interaction among Mxi1, miR-300 and KLF9. Loss- and gain-of-function studies were conducted to determine the roles of Mxi1, miR-300, and KLF9 in cell proliferation, migration, and invasion in vitro and their effects on myeloid-derived suppressor cell (MDSC) recruitment in vivo. Mxi1 was poorly expressed in lung cancer tissues and cells and its poor expression was associated with poor prognosis. Mxi1 inhibited miR-300 by suppressing its transcription. miR-300 suppressed the expression of KLF9, and KLF9 negatively regulated GADD34 expression in lung cancer cells. Mxi1 or KLF9 elevation or miR-300 repression inhibited lung cancer cell proliferation, as evidenced by reduced Ki67 and PCNA expression, and lowered invasion and migration. In vivo findings revealed that silencing KLF9 induced tumor growth by enhancing MDSC-mediated immunosuppression through upregulation of GADD34. Collectively, these findings suggest that Mxi1 can inhibit lung cancer progression by regulating the miR-300/KLF9 axis and GADD34-mediated immunosuppression. |
format | Online Article Text |
id | pubmed-9061846 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-90618462022-05-04 Mxi1 participates in the progression of lung cancer via the microRNA-300/KLF9/GADD34 Axis Lei, Yujie Huang, Yunchao Lin, Jianbin Sun, Shihui Che, Keda Shen, Junting Liao, Jun Chen, Yangming Chen, Kai Lin, Zhaoxian Lin, Xing Cell Death Dis Article The purpose of the current study was to define the role of MAX interactor 1 (Mxi1) in the pathogenesis of lung cancer and its underlying molecular mechanism. Bioinformatics analysis was performed to identify important regulatory pathway related to lung cancer. Dual luciferase reporter and ChIP assays were adopted to validate the interaction among Mxi1, miR-300 and KLF9. Loss- and gain-of-function studies were conducted to determine the roles of Mxi1, miR-300, and KLF9 in cell proliferation, migration, and invasion in vitro and their effects on myeloid-derived suppressor cell (MDSC) recruitment in vivo. Mxi1 was poorly expressed in lung cancer tissues and cells and its poor expression was associated with poor prognosis. Mxi1 inhibited miR-300 by suppressing its transcription. miR-300 suppressed the expression of KLF9, and KLF9 negatively regulated GADD34 expression in lung cancer cells. Mxi1 or KLF9 elevation or miR-300 repression inhibited lung cancer cell proliferation, as evidenced by reduced Ki67 and PCNA expression, and lowered invasion and migration. In vivo findings revealed that silencing KLF9 induced tumor growth by enhancing MDSC-mediated immunosuppression through upregulation of GADD34. Collectively, these findings suggest that Mxi1 can inhibit lung cancer progression by regulating the miR-300/KLF9 axis and GADD34-mediated immunosuppression. Nature Publishing Group UK 2022-05-02 /pmc/articles/PMC9061846/ /pubmed/35501353 http://dx.doi.org/10.1038/s41419-022-04778-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Lei, Yujie Huang, Yunchao Lin, Jianbin Sun, Shihui Che, Keda Shen, Junting Liao, Jun Chen, Yangming Chen, Kai Lin, Zhaoxian Lin, Xing Mxi1 participates in the progression of lung cancer via the microRNA-300/KLF9/GADD34 Axis |
title | Mxi1 participates in the progression of lung cancer via the microRNA-300/KLF9/GADD34 Axis |
title_full | Mxi1 participates in the progression of lung cancer via the microRNA-300/KLF9/GADD34 Axis |
title_fullStr | Mxi1 participates in the progression of lung cancer via the microRNA-300/KLF9/GADD34 Axis |
title_full_unstemmed | Mxi1 participates in the progression of lung cancer via the microRNA-300/KLF9/GADD34 Axis |
title_short | Mxi1 participates in the progression of lung cancer via the microRNA-300/KLF9/GADD34 Axis |
title_sort | mxi1 participates in the progression of lung cancer via the microrna-300/klf9/gadd34 axis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9061846/ https://www.ncbi.nlm.nih.gov/pubmed/35501353 http://dx.doi.org/10.1038/s41419-022-04778-w |
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