Cargando…
Transcription factor CDX2 up-regulates proto-oncogenic miR-744 via a promoter activation mechanism in non-small-cell lung cancer
BACKGROUND: The role of caudal-related homeobox 2 (CDX2) in the pathogenesis of non-small cell lung cancer (NSCLC) is unclear. The purpose of this study was to investigate the mRNA (message RNA) expression of CDX2 in NSCLC, and to determine its relationship with miR-744 (microRNA744) and its potenti...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576675/ https://www.ncbi.nlm.nih.gov/pubmed/34790744 http://dx.doi.org/10.21037/atm-21-4526 |
_version_ | 1784595924484358144 |
---|---|
author | Sha, Zhou Hao, Song Long, Fengjiao Wei, Yajun Chen, Shaoyi Li, Ting Yi, Lina Hu, Liyang Lin, Zhong Xian, Jianzhong Pei, Xiaofeng |
author_facet | Sha, Zhou Hao, Song Long, Fengjiao Wei, Yajun Chen, Shaoyi Li, Ting Yi, Lina Hu, Liyang Lin, Zhong Xian, Jianzhong Pei, Xiaofeng |
author_sort | Sha, Zhou |
collection | PubMed |
description | BACKGROUND: The role of caudal-related homeobox 2 (CDX2) in the pathogenesis of non-small cell lung cancer (NSCLC) is unclear. The purpose of this study was to investigate the mRNA (message RNA) expression of CDX2 in NSCLC, and to determine its relationship with miR-744 (microRNA744) and its potential as a biomarker of NSCLC. METHODS: MiR-744 is overexpressed in A549, H460, and H1299 cell lines. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression. A chromatin immunoprecipitation (ChIP) essay was performed to determine the CDX2 binding sites. We then conducted a luciferase reporter essay to analyze interaction between MiR-744 and 3'UTRs (the 3' untranslated sequences). The migration and Boyden chamber method were used to study cell mobility. RESULTS: In this study, we found that ectopic CDX2 increased the expression of miR-744, while the attenuation of CDX2 reduced the expression of miR-744 by qRT-PCR. Chromatin immunoprecipitation experiments confirmed that CDX2 directly binds to the promoter of miR-744. The luciferase reporter assay further verified the binding sites of −347 to −358 bp in the most likely promoter like sequence of miR-744. CDX2-induced up-regulation of miR-744 can significantly promote the migration and invasion of NSCLC cells, while overexpression CDX2 is sufficient to rescue the migration and invasion capacity of these cells following knockdown of miR-744. CONCLUSIONS: In summary, our results confirmed for the first time the regulatory mechanism of CDX2 on miR-744 transcription and provided a potential mechanism for CDX2 as an oncogene in lung cancer. |
format | Online Article Text |
id | pubmed-8576675 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-85766752021-11-16 Transcription factor CDX2 up-regulates proto-oncogenic miR-744 via a promoter activation mechanism in non-small-cell lung cancer Sha, Zhou Hao, Song Long, Fengjiao Wei, Yajun Chen, Shaoyi Li, Ting Yi, Lina Hu, Liyang Lin, Zhong Xian, Jianzhong Pei, Xiaofeng Ann Transl Med Original Article BACKGROUND: The role of caudal-related homeobox 2 (CDX2) in the pathogenesis of non-small cell lung cancer (NSCLC) is unclear. The purpose of this study was to investigate the mRNA (message RNA) expression of CDX2 in NSCLC, and to determine its relationship with miR-744 (microRNA744) and its potential as a biomarker of NSCLC. METHODS: MiR-744 is overexpressed in A549, H460, and H1299 cell lines. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression. A chromatin immunoprecipitation (ChIP) essay was performed to determine the CDX2 binding sites. We then conducted a luciferase reporter essay to analyze interaction between MiR-744 and 3'UTRs (the 3' untranslated sequences). The migration and Boyden chamber method were used to study cell mobility. RESULTS: In this study, we found that ectopic CDX2 increased the expression of miR-744, while the attenuation of CDX2 reduced the expression of miR-744 by qRT-PCR. Chromatin immunoprecipitation experiments confirmed that CDX2 directly binds to the promoter of miR-744. The luciferase reporter assay further verified the binding sites of −347 to −358 bp in the most likely promoter like sequence of miR-744. CDX2-induced up-regulation of miR-744 can significantly promote the migration and invasion of NSCLC cells, while overexpression CDX2 is sufficient to rescue the migration and invasion capacity of these cells following knockdown of miR-744. CONCLUSIONS: In summary, our results confirmed for the first time the regulatory mechanism of CDX2 on miR-744 transcription and provided a potential mechanism for CDX2 as an oncogene in lung cancer. AME Publishing Company 2021-10 /pmc/articles/PMC8576675/ /pubmed/34790744 http://dx.doi.org/10.21037/atm-21-4526 Text en 2021 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Sha, Zhou Hao, Song Long, Fengjiao Wei, Yajun Chen, Shaoyi Li, Ting Yi, Lina Hu, Liyang Lin, Zhong Xian, Jianzhong Pei, Xiaofeng Transcription factor CDX2 up-regulates proto-oncogenic miR-744 via a promoter activation mechanism in non-small-cell lung cancer |
title | Transcription factor CDX2 up-regulates proto-oncogenic miR-744 via a promoter activation mechanism in non-small-cell lung cancer |
title_full | Transcription factor CDX2 up-regulates proto-oncogenic miR-744 via a promoter activation mechanism in non-small-cell lung cancer |
title_fullStr | Transcription factor CDX2 up-regulates proto-oncogenic miR-744 via a promoter activation mechanism in non-small-cell lung cancer |
title_full_unstemmed | Transcription factor CDX2 up-regulates proto-oncogenic miR-744 via a promoter activation mechanism in non-small-cell lung cancer |
title_short | Transcription factor CDX2 up-regulates proto-oncogenic miR-744 via a promoter activation mechanism in non-small-cell lung cancer |
title_sort | transcription factor cdx2 up-regulates proto-oncogenic mir-744 via a promoter activation mechanism in non-small-cell lung cancer |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576675/ https://www.ncbi.nlm.nih.gov/pubmed/34790744 http://dx.doi.org/10.21037/atm-21-4526 |
work_keys_str_mv | AT shazhou transcriptionfactorcdx2upregulatesprotooncogenicmir744viaapromoteractivationmechanisminnonsmallcelllungcancer AT haosong transcriptionfactorcdx2upregulatesprotooncogenicmir744viaapromoteractivationmechanisminnonsmallcelllungcancer AT longfengjiao transcriptionfactorcdx2upregulatesprotooncogenicmir744viaapromoteractivationmechanisminnonsmallcelllungcancer AT weiyajun transcriptionfactorcdx2upregulatesprotooncogenicmir744viaapromoteractivationmechanisminnonsmallcelllungcancer AT chenshaoyi transcriptionfactorcdx2upregulatesprotooncogenicmir744viaapromoteractivationmechanisminnonsmallcelllungcancer AT liting transcriptionfactorcdx2upregulatesprotooncogenicmir744viaapromoteractivationmechanisminnonsmallcelllungcancer AT yilina transcriptionfactorcdx2upregulatesprotooncogenicmir744viaapromoteractivationmechanisminnonsmallcelllungcancer AT huliyang transcriptionfactorcdx2upregulatesprotooncogenicmir744viaapromoteractivationmechanisminnonsmallcelllungcancer AT linzhong transcriptionfactorcdx2upregulatesprotooncogenicmir744viaapromoteractivationmechanisminnonsmallcelllungcancer AT xianjianzhong transcriptionfactorcdx2upregulatesprotooncogenicmir744viaapromoteractivationmechanisminnonsmallcelllungcancer AT peixiaofeng transcriptionfactorcdx2upregulatesprotooncogenicmir744viaapromoteractivationmechanisminnonsmallcelllungcancer |