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.
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This is a list of supplementary files associated with this preprint. Click to download.
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.
Supplementary Fig. S2 Correlation analysis of GAP43 expression level and its promoter methylation level in colon adenocarcinoma (a) and rectal adenocarcinoma (b).
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.
Supplementary Table S1 Quality Control (QC) of our RNA-seq data.
Supplementary Table S2 GAP43 overexpression related genes revealed by RNA-seq. (p-value<0.05)
Supplementary Table S3 DAVID analysis (GO_BP) of GAP43 overexpression related genes (p-value < 0.05).
Supplementary Table S4 DAVID analysis (KEGG) of GAP43 overexpression related genes (p-value < 0.05).
Supplementary Table S5 IPA Canonical Pathways of GAP43 overexpression related genes.
Supplementary Table S6 Primers for qRT-PCR.
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Posted 23 Sep, 2020
On 05 Jan, 2021
On 05 Jan, 2021
Received 26 Oct, 2020
On 26 Oct, 2020
Received 16 Oct, 2020
On 05 Oct, 2020
On 04 Oct, 2020
Invitations sent on 22 Sep, 2020
On 22 Sep, 2020
On 10 Sep, 2020
On 09 Sep, 2020
On 09 Sep, 2020
On 08 Sep, 2020
Posted 23 Sep, 2020
On 05 Jan, 2021
On 05 Jan, 2021
Received 26 Oct, 2020
On 26 Oct, 2020
Received 16 Oct, 2020
On 05 Oct, 2020
On 04 Oct, 2020
Invitations sent on 22 Sep, 2020
On 22 Sep, 2020
On 10 Sep, 2020
On 09 Sep, 2020
On 09 Sep, 2020
On 08 Sep, 2020
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
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