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Transcriptome profiling unveils GAP43 regulates ABC transporters and EIF2 signaling in colorectal cancer cells

BACKGROUND: The growth- and plasticity-associated protein-43 (GAP43) is biasedly expressed in indigestive system and nervous system. Recent study has shown that GAP43 is responsible for the development of neuronal growth and axonal regeneration in normal nervous tissue, while serves as a specific bi...

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Autores principales: Chen, Xi, Wu, Hongjin, Feng, Jia, Li, Ying, Lv, Jiao, Shi, Weikai, Fan, Weiwei, Xiao, Li, Sun, Danmeng, Jiang, Mingfeng, Shi, Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786480/
https://www.ncbi.nlm.nih.gov/pubmed/33402155
http://dx.doi.org/10.1186/s12885-020-07728-x
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author Chen, Xi
Wu, Hongjin
Feng, Jia
Li, Ying
Lv, Jiao
Shi, Weikai
Fan, Weiwei
Xiao, Li
Sun, Danmeng
Jiang, Mingfeng
Shi, Ming
author_facet Chen, Xi
Wu, Hongjin
Feng, Jia
Li, Ying
Lv, Jiao
Shi, Weikai
Fan, Weiwei
Xiao, Li
Sun, Danmeng
Jiang, Mingfeng
Shi, Ming
author_sort Chen, Xi
collection PubMed
description BACKGROUND: The growth- and plasticity-associated protein-43 (GAP43) is biasedly expressed in indigestive system and nervous system. Recent study has shown that GAP43 is responsible for the development of neuronal growth and axonal regeneration in normal nervous tissue, while serves as a specific biomarker of relapsed or refractory neuroblastoma. However, its expression pattern and function in digestive system cancer remains to be clarified. METHODS: In this study, we examined the GAP43 status with qRT-PCR and bisulfite genomic sequencing in colorectal cancer (CRC). We investigated the effect of overexpressed GAP43 in CRC cells with RNA-seq. The RNA-seq data was analyzed with DAVID and IPA. RESULTS: GAP43 was downregulated in CRC compared to the adjacent tissues. DNA methylase inhibitor 5-Aza-CdR treatment could significantly induce GAP43, indicated that the silencing of GAP43 gene in CRC is closely related to DNA methylation. Bisulfite genomic sequencing confirmed the promoter methylation of GAP43 in CRC. To explore the transcriptional alterations by overexpressed GAP43 in CRC, we performed RNA-seq and found that upregulated genes were significantly enriched in the signaling pathways of ABC transporters and ECM-receptor interaction, while downregulated genes were significantly enriched in Ribosome signaling pathway. Further Ingenuity Pathway Analysis (IPA) showed that EIF2 signaling pathway was significantly repressed by overexpression of GAP43. CONCLUSION: Our findings provide a novel mechanistic insight of GAP43 in CRC. Transcriptome profiling of overexpressed GAP43 in CRC uncovered the functional roles of GAP43 in the development of human CRC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-020-07728-x.
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spelling pubmed-77864802021-01-07 Transcriptome profiling unveils GAP43 regulates ABC transporters and EIF2 signaling in colorectal cancer cells Chen, Xi Wu, Hongjin Feng, Jia Li, Ying Lv, Jiao Shi, Weikai Fan, Weiwei Xiao, Li Sun, Danmeng Jiang, Mingfeng Shi, Ming BMC Cancer Research Article BACKGROUND: The growth- and plasticity-associated protein-43 (GAP43) is biasedly expressed in indigestive system and nervous system. Recent study has shown that GAP43 is responsible for the development of neuronal growth and axonal regeneration in normal nervous tissue, while serves as a specific biomarker of relapsed or refractory neuroblastoma. However, its expression pattern and function in digestive system cancer remains to be clarified. METHODS: In this study, we examined the GAP43 status with qRT-PCR and bisulfite genomic sequencing in colorectal cancer (CRC). We investigated the effect of overexpressed GAP43 in CRC cells with RNA-seq. The RNA-seq data was analyzed with DAVID and IPA. RESULTS: GAP43 was downregulated in CRC compared to the adjacent tissues. DNA methylase inhibitor 5-Aza-CdR treatment could significantly induce GAP43, indicated that the silencing of GAP43 gene in CRC is closely related to DNA methylation. Bisulfite genomic sequencing confirmed the promoter methylation of GAP43 in CRC. To explore the transcriptional alterations by overexpressed GAP43 in CRC, we performed RNA-seq and found that upregulated genes were significantly enriched in the signaling pathways of ABC transporters and ECM-receptor interaction, while downregulated genes were significantly enriched in Ribosome signaling pathway. Further Ingenuity Pathway Analysis (IPA) showed that EIF2 signaling pathway was significantly repressed by overexpression of GAP43. CONCLUSION: Our findings provide a novel mechanistic insight of GAP43 in CRC. Transcriptome profiling of overexpressed GAP43 in CRC uncovered the functional roles of GAP43 in the development of human CRC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-020-07728-x. BioMed Central 2021-01-05 /pmc/articles/PMC7786480/ /pubmed/33402155 http://dx.doi.org/10.1186/s12885-020-07728-x Text en © The Author(s) 2021 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Chen, Xi
Wu, Hongjin
Feng, Jia
Li, Ying
Lv, Jiao
Shi, Weikai
Fan, Weiwei
Xiao, Li
Sun, Danmeng
Jiang, Mingfeng
Shi, Ming
Transcriptome profiling unveils GAP43 regulates ABC transporters and EIF2 signaling in colorectal cancer cells
title Transcriptome profiling unveils GAP43 regulates ABC transporters and EIF2 signaling in colorectal cancer cells
title_full Transcriptome profiling unveils GAP43 regulates ABC transporters and EIF2 signaling in colorectal cancer cells
title_fullStr Transcriptome profiling unveils GAP43 regulates ABC transporters and EIF2 signaling in colorectal cancer cells
title_full_unstemmed Transcriptome profiling unveils GAP43 regulates ABC transporters and EIF2 signaling in colorectal cancer cells
title_short Transcriptome profiling unveils GAP43 regulates ABC transporters and EIF2 signaling in colorectal cancer cells
title_sort transcriptome profiling unveils gap43 regulates abc transporters and eif2 signaling in colorectal cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786480/
https://www.ncbi.nlm.nih.gov/pubmed/33402155
http://dx.doi.org/10.1186/s12885-020-07728-x
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