See the published version of this preprint at BMC Cancer.
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Research article
MING SHI
Harbin Institute of Technology
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0527-0061
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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 still remains to be clarified.
Results
In this study, we found GAP43 was downregulated in colorectal cancer (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 and histone deacetylation. 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.
Keywords
GAP43, Colorectal cancer, RNA-seq, DNA methylation, Transcriptome profiling.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
- FigureS1.pdf
Supplementary Fig. S1 Mutation and expression level analysis of GAP43 in CRC tissues with online database. a Mutation level of GAP43 in CRC tissues with cBioPortal database. b Expression level of GAP43 in CRC tissues with Oncomine database.
- FigureS2.pdf
Supplementary Fig. S2 Correlation analysis of GAP43 expression level and its promoter methylation level in colon adenocarcinoma (a) and rectal adenocarcinoma (b).
- FigureS3.pdf
Supplementary Fig. S3 Kaplan-Meier Plotter survival analysis of GAP43 in gastric cancer with or without different treatments. a gastric cancer. b gastric cancer with surgery only. c gastric cancer with 5-FU based adjuvant.
- SupplementaryTableS1.xlsx
Supplementary Table S1 Quality Control (QC) of our RNA-seq data.
- SupplementaryTableS2.xlsx
Supplementary Table S2 GAP43 overexpression related genes revealed by RNA-seq. (p-value<0.05)
- SupplementaryTableS3.xlsx
Supplementary Table S3 DAVID analysis (GO_BP) of GAP43 overexpression related genes (p-value < 0.05).
- SupplementaryTableS4.xlsx
Supplementary Table S4 DAVID analysis (KEGG) of GAP43 overexpression related genes (p-value < 0.05).
- SupplementaryTableS5.xlsx
Supplementary Table S5 IPA Canonical Pathways of GAP43 overexpression related genes.
- SupplementaryTableS6.xlsx
Supplementary Table S6 Primers for qRT-PCR.
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CURRENT STATUS: Published
View the published article at BMC Cancer.
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Posted 23 Sep, 2020
No community comments so far
Review #2 received
Received 26 Oct, 2020
Editorial decision: Major revision
On 26 Oct, 2020
Review #1 received
Received 16 Oct, 2020
Reviewer #3 agreed
On 05 Oct, 2020
Reviewer #2 agreed
On 04 Oct, 2020
Reviewers invited
Invitations sent on 22 Sep, 2020
Reviewer #1 agreed
On 22 Sep, 2020
Editor assigned
On 10 Sep, 2020
Submission checks complete
On 09 Sep, 2020
Editor invited
On 09 Sep, 2020
First submitted
On 08 Sep, 2020
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Learn more about our company.
See the published version of this preprint at BMC Cancer.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
MING SHI
Harbin Institute of Technology
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0527-0061
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BMC Cancer.
Version 1
Posted 23 Sep, 2020
No community comments so far
Review #2 received
Received 26 Oct, 2020
Editorial decision: Major revision
On 26 Oct, 2020
Review #1 received
Received 16 Oct, 2020
Reviewer #3 agreed
On 05 Oct, 2020
Reviewer #2 agreed
On 04 Oct, 2020
Reviewers invited
Invitations sent on 22 Sep, 2020
Reviewer #1 agreed
On 22 Sep, 2020
Editor assigned
On 10 Sep, 2020
Submission checks complete
On 09 Sep, 2020
Editor invited
On 09 Sep, 2020
First submitted
On 08 Sep, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Cancer.
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 still remains to be clarified.
Results
In this study, we found GAP43 was downregulated in colorectal cancer (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 and histone deacetylation. 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.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
- FigureS1.pdf
Supplementary Fig. S1 Mutation and expression level analysis of GAP43 in CRC tissues with online database. a Mutation level of GAP43 in CRC tissues with cBioPortal database. b Expression level of GAP43 in CRC tissues with Oncomine database.
- FigureS2.pdf
Supplementary Fig. S2 Correlation analysis of GAP43 expression level and its promoter methylation level in colon adenocarcinoma (a) and rectal adenocarcinoma (b).
- FigureS3.pdf
Supplementary Fig. S3 Kaplan-Meier Plotter survival analysis of GAP43 in gastric cancer with or without different treatments. a gastric cancer. b gastric cancer with surgery only. c gastric cancer with 5-FU based adjuvant.
- SupplementaryTableS1.xlsx
Supplementary Table S1 Quality Control (QC) of our RNA-seq data.
- SupplementaryTableS2.xlsx
Supplementary Table S2 GAP43 overexpression related genes revealed by RNA-seq. (p-value<0.05)
- SupplementaryTableS3.xlsx
Supplementary Table S3 DAVID analysis (GO_BP) of GAP43 overexpression related genes (p-value < 0.05).
- SupplementaryTableS4.xlsx
Supplementary Table S4 DAVID analysis (KEGG) of GAP43 overexpression related genes (p-value < 0.05).
- SupplementaryTableS5.xlsx
Supplementary Table S5 IPA Canonical Pathways of GAP43 overexpression related genes.
- SupplementaryTableS6.xlsx
Supplementary Table S6 Primers for qRT-PCR.
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