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TSPAN1-elevated FAM110A promotes pancreatic cancer progression by transcriptionally regulating HIST1H2BK
Background: FAM110A belongs to the FAM110 family, which mainly functions in biological processes associated with the cell cycle. However, the biological functions in which FAM110A participates are largely undefined. In particular, its potential role in cancer remains unknown. The goal of this study...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824879/ https://www.ncbi.nlm.nih.gov/pubmed/35154458 http://dx.doi.org/10.7150/jca.66404 |
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author | Huang, Hua Li, Huan Zhao, Ting Khan, Aamir Ali Pan, Ruining Wang, Sijia Wang, Shensen Liu, Xinhui |
author_facet | Huang, Hua Li, Huan Zhao, Ting Khan, Aamir Ali Pan, Ruining Wang, Sijia Wang, Shensen Liu, Xinhui |
author_sort | Huang, Hua |
collection | PubMed |
description | Background: FAM110A belongs to the FAM110 family, which mainly functions in biological processes associated with the cell cycle. However, the biological functions in which FAM110A participates are largely undefined. In particular, its potential role in cancer remains unknown. The goal of this study was to uncover the role and mechanism of FAM110A in pancreatic cancer. Methods: Based on bioinformatics databases, qPCR and Western blot assays, we verified the elevated expression level of FAM110A in PDAC. Subsequently, FAM110A, HIST1H2BK and TSPAN1 overexpression or knockdown stable transfected cells were employed for biological functions' studies to explore the role in PDAC in vitro and in vivo. RNA-Seq, Western blot and luciferase-reporter assays were used to explore mechanism of FAM110A action in PDAC, and the involved pathway was verified by tumor phenotypic rescue experiments. Results: In this study, we demonstrated for the first time that FAM110A is an oncogene that promotes cell proliferation, migration, invasion and tumorigenesis in pancreatic cancer. HIST1H2BK was identified as the downstream target of FAM110A, while the promotion effect caused by FAM110A overexpression could be abolished by HIST1H2BK knockdown. Moreover, for the first time, we revealed the oncogenic role of HIST1H2BK in pancreatic cancer, and the tumor-promoting capacity of HIST1H2BK may be associated with its regulatory effect on G9a. In addition, we demonstrated that TSPAN1 displayed a positive transcriptional regulatory effect on FAM110A. Conclusions: Collectively, FAM110A plays an oncogenic role in PDAC, and the newly identified TSPAN1/FAM110A/HIST1H2BK/G9a pathway is involved in the modulation of pancreatic cancer progression and provides a novel prognostic and therapeutic strategy for pancreatic cancer treatment. |
format | Online Article Text |
id | pubmed-8824879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-88248792022-02-11 TSPAN1-elevated FAM110A promotes pancreatic cancer progression by transcriptionally regulating HIST1H2BK Huang, Hua Li, Huan Zhao, Ting Khan, Aamir Ali Pan, Ruining Wang, Sijia Wang, Shensen Liu, Xinhui J Cancer Research Paper Background: FAM110A belongs to the FAM110 family, which mainly functions in biological processes associated with the cell cycle. However, the biological functions in which FAM110A participates are largely undefined. In particular, its potential role in cancer remains unknown. The goal of this study was to uncover the role and mechanism of FAM110A in pancreatic cancer. Methods: Based on bioinformatics databases, qPCR and Western blot assays, we verified the elevated expression level of FAM110A in PDAC. Subsequently, FAM110A, HIST1H2BK and TSPAN1 overexpression or knockdown stable transfected cells were employed for biological functions' studies to explore the role in PDAC in vitro and in vivo. RNA-Seq, Western blot and luciferase-reporter assays were used to explore mechanism of FAM110A action in PDAC, and the involved pathway was verified by tumor phenotypic rescue experiments. Results: In this study, we demonstrated for the first time that FAM110A is an oncogene that promotes cell proliferation, migration, invasion and tumorigenesis in pancreatic cancer. HIST1H2BK was identified as the downstream target of FAM110A, while the promotion effect caused by FAM110A overexpression could be abolished by HIST1H2BK knockdown. Moreover, for the first time, we revealed the oncogenic role of HIST1H2BK in pancreatic cancer, and the tumor-promoting capacity of HIST1H2BK may be associated with its regulatory effect on G9a. In addition, we demonstrated that TSPAN1 displayed a positive transcriptional regulatory effect on FAM110A. Conclusions: Collectively, FAM110A plays an oncogenic role in PDAC, and the newly identified TSPAN1/FAM110A/HIST1H2BK/G9a pathway is involved in the modulation of pancreatic cancer progression and provides a novel prognostic and therapeutic strategy for pancreatic cancer treatment. Ivyspring International Publisher 2022-01-01 /pmc/articles/PMC8824879/ /pubmed/35154458 http://dx.doi.org/10.7150/jca.66404 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 Huang, Hua Li, Huan Zhao, Ting Khan, Aamir Ali Pan, Ruining Wang, Sijia Wang, Shensen Liu, Xinhui TSPAN1-elevated FAM110A promotes pancreatic cancer progression by transcriptionally regulating HIST1H2BK |
title | TSPAN1-elevated FAM110A promotes pancreatic cancer progression by transcriptionally regulating HIST1H2BK |
title_full | TSPAN1-elevated FAM110A promotes pancreatic cancer progression by transcriptionally regulating HIST1H2BK |
title_fullStr | TSPAN1-elevated FAM110A promotes pancreatic cancer progression by transcriptionally regulating HIST1H2BK |
title_full_unstemmed | TSPAN1-elevated FAM110A promotes pancreatic cancer progression by transcriptionally regulating HIST1H2BK |
title_short | TSPAN1-elevated FAM110A promotes pancreatic cancer progression by transcriptionally regulating HIST1H2BK |
title_sort | tspan1-elevated fam110a promotes pancreatic cancer progression by transcriptionally regulating hist1h2bk |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8824879/ https://www.ncbi.nlm.nih.gov/pubmed/35154458 http://dx.doi.org/10.7150/jca.66404 |
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