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Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR
Objective: Fhit gene is known as a genome “caretaker” and frequently inactivated by deletion or hypermethylation on the promoter in several cancers. In spite of several lines of evidence, the exact mechanism underlying Fhit-induced biology is relatively less studied. This study will focus the role o...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797533/ https://www.ncbi.nlm.nih.gov/pubmed/33437205 http://dx.doi.org/10.7150/ijms.51429 |
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author | Chae, Hae-Jung Seo, Jong Bae Kim, Sung-Hak Jeon, Young-Jun Suh, Sung-Suk |
author_facet | Chae, Hae-Jung Seo, Jong Bae Kim, Sung-Hak Jeon, Young-Jun Suh, Sung-Suk |
author_sort | Chae, Hae-Jung |
collection | PubMed |
description | Objective: Fhit gene is known as a genome “caretaker” and frequently inactivated by deletion or hypermethylation on the promoter in several cancers. In spite of several lines of evidence, the exact mechanism underlying Fhit-induced biology is relatively less studied. This study will focus the role of Fhit in regulating Lin28 and microRNAs (miRNAs) loop. Material and Methods: To this end, we employed Fhit overexpressing isogenic cell lines to conduct miRNA nanostring array, and differentially expressed miRNAs were identified. Using real-time PCR and Western blot analysis, expression levels of Lin28b or miRNAs were investigated in response to the overexpression of Fhit gene in H1299 lung cancer cells. Results: A series of in vitro including gene nanostring analyses revealed that Lin28B protein was induced by Fhit gene overexpression, which consequently suppressed Let-7 miRNAs. Also, we found that miRNAs in miR-17/92 clusters are redundantly increased and there is an inverse correlation between Let-7 and miR-17/92 clusters in Fhit-expressing cells. Also, a series of in vitro experiments suggests that ELF-1- and/or STAT1-dependent Lin28b regulation is responsible for Let-7 induction in Fhit-expressing cancer cells. Conclusions: Based on the same experimental system proving that Fhit gene has a robust role in suppressing tumor progression and epithelial-mesenchymal transition, our data show that Fhit mediates the negative feedback between Lin28/Let-7 axis and miR-17/-92 miRNA although the physiological relevance of current interesting observation should be further investigated. |
format | Online Article Text |
id | pubmed-7797533 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-77975332021-01-11 Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR Chae, Hae-Jung Seo, Jong Bae Kim, Sung-Hak Jeon, Young-Jun Suh, Sung-Suk Int J Med Sci Research Paper Objective: Fhit gene is known as a genome “caretaker” and frequently inactivated by deletion or hypermethylation on the promoter in several cancers. In spite of several lines of evidence, the exact mechanism underlying Fhit-induced biology is relatively less studied. This study will focus the role of Fhit in regulating Lin28 and microRNAs (miRNAs) loop. Material and Methods: To this end, we employed Fhit overexpressing isogenic cell lines to conduct miRNA nanostring array, and differentially expressed miRNAs were identified. Using real-time PCR and Western blot analysis, expression levels of Lin28b or miRNAs were investigated in response to the overexpression of Fhit gene in H1299 lung cancer cells. Results: A series of in vitro including gene nanostring analyses revealed that Lin28B protein was induced by Fhit gene overexpression, which consequently suppressed Let-7 miRNAs. Also, we found that miRNAs in miR-17/92 clusters are redundantly increased and there is an inverse correlation between Let-7 and miR-17/92 clusters in Fhit-expressing cells. Also, a series of in vitro experiments suggests that ELF-1- and/or STAT1-dependent Lin28b regulation is responsible for Let-7 induction in Fhit-expressing cancer cells. Conclusions: Based on the same experimental system proving that Fhit gene has a robust role in suppressing tumor progression and epithelial-mesenchymal transition, our data show that Fhit mediates the negative feedback between Lin28/Let-7 axis and miR-17/-92 miRNA although the physiological relevance of current interesting observation should be further investigated. Ivyspring International Publisher 2021-01-01 /pmc/articles/PMC7797533/ /pubmed/33437205 http://dx.doi.org/10.7150/ijms.51429 Text en © The author(s) 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 Chae, Hae-Jung Seo, Jong Bae Kim, Sung-Hak Jeon, Young-Jun Suh, Sung-Suk Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR |
title | Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR |
title_full | Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR |
title_fullStr | Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR |
title_full_unstemmed | Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR |
title_short | Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR |
title_sort | fhit induces the reciprocal suppressions between lin28/let-7 and mir-17/92mir |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797533/ https://www.ncbi.nlm.nih.gov/pubmed/33437205 http://dx.doi.org/10.7150/ijms.51429 |
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