Comprehensive RNAseq analysis reveals PIK3CD promotes glioblastoma tumorigenesis by mediating PI3K-Akt signaling pathway
Background and Aim: Glioblastoma (GBM) is the most common and aggressive form of primary malignant brain tumors. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD), which is overexpressed in GBM, is involved in GBM pathogenesis and drug resistance. However, the molecular...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2020-01-01
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| Series: | Glioma |
| Subjects: | |
| Online Access: | http://www.jglioma.com/article.asp?issn=2589-6113;year=2020;volume=3;issue=3;spage=135;epage=142;aulast= |
| _version_ | 1818342750389534720 |
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| author | Zulfikar Azam Wei Shao Ho-keung Ng Jing Wang Zhong-ping Chen Shing-shun Tony To |
| author_facet | Zulfikar Azam Wei Shao Ho-keung Ng Jing Wang Zhong-ping Chen Shing-shun Tony To |
| author_sort | Zulfikar Azam |
| collection | DOAJ |
| description | Background and Aim: Glioblastoma (GBM) is the most common and aggressive form of primary malignant brain tumors. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD), which is overexpressed in GBM, is involved in GBM pathogenesis and drug resistance. However, the molecular mechanism by which PIK3CD drives its transcriptional program toward GBM favors remains elusive. Materials and Methods: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated 9 technology was used to knock-out (KO) PIK3CD gene, and comprehensive RNAseq analysis was performed to investigate the underlying role of PIK3CD in GBM. Results: To minimize the off-target effects, two KO cell clones were used, and our data showed that PIK3CD KO altered the expression 306 genes in both KO cell clones compared with the parent U87 cell line. Gene set enrichment analysis revealed that genes involved in epithelial-mesenchymal (MES) transition-related biological processes were highly depressed in both KO cell clones in a similar fashion, suggesting PIK3CD's involvement in MES transformation/transition in GBM. Comprehensive pathway analysis by three different platforms confirmed that PIK3CD exerted its oncogenic function in GBM through phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway. In addition, other signaling pathways (integrin, cadherin, Wnt, and inflammation mediated by chemokine and cytokine signaling pathways) were found decreased in the KO cell clones. Further, The Cancer Genomic Atlas (TCGA) analysis of our PI3K-Akt pathway-related genes showed a similar pattern of expression. Conclusion: PIK3CD is involved in GBM pathogenesis, and this action probably mediated through the PI3K-Akt signaling pathway. |
| first_indexed | 2024-12-13T16:19:39Z |
| format | Article |
| id | doaj.art-40c6f5fcdd3c48288feb86b16719dc72 |
| institution | Directory Open Access Journal |
| issn | 2589-6113 2589-6121 |
| language | English |
| last_indexed | 2024-12-13T16:19:39Z |
| publishDate | 2020-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Glioma |
| spelling | doaj.art-40c6f5fcdd3c48288feb86b16719dc722022-12-21T23:38:45ZengWolters Kluwer Medknow PublicationsGlioma2589-61132589-61212020-01-013313514210.4103/glioma.glioma_23_20Comprehensive RNAseq analysis reveals PIK3CD promotes glioblastoma tumorigenesis by mediating PI3K-Akt signaling pathwayZulfikar AzamWei ShaoHo-keung NgJing WangZhong-ping ChenShing-shun Tony ToBackground and Aim: Glioblastoma (GBM) is the most common and aggressive form of primary malignant brain tumors. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (PIK3CD), which is overexpressed in GBM, is involved in GBM pathogenesis and drug resistance. However, the molecular mechanism by which PIK3CD drives its transcriptional program toward GBM favors remains elusive. Materials and Methods: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated 9 technology was used to knock-out (KO) PIK3CD gene, and comprehensive RNAseq analysis was performed to investigate the underlying role of PIK3CD in GBM. Results: To minimize the off-target effects, two KO cell clones were used, and our data showed that PIK3CD KO altered the expression 306 genes in both KO cell clones compared with the parent U87 cell line. Gene set enrichment analysis revealed that genes involved in epithelial-mesenchymal (MES) transition-related biological processes were highly depressed in both KO cell clones in a similar fashion, suggesting PIK3CD's involvement in MES transformation/transition in GBM. Comprehensive pathway analysis by three different platforms confirmed that PIK3CD exerted its oncogenic function in GBM through phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway. In addition, other signaling pathways (integrin, cadherin, Wnt, and inflammation mediated by chemokine and cytokine signaling pathways) were found decreased in the KO cell clones. Further, The Cancer Genomic Atlas (TCGA) analysis of our PI3K-Akt pathway-related genes showed a similar pattern of expression. Conclusion: PIK3CD is involved in GBM pathogenesis, and this action probably mediated through the PI3K-Akt signaling pathway.http://www.jglioma.com/article.asp?issn=2589-6113;year=2020;volume=3;issue=3;spage=135;epage=142;aulast=glioblastomaintegrinmesenchymal transformationphosphatidylinositol 3-kinase-aktphosphatidylinositol-45-bisphosphate 3-kinase catalytic subunit delta knock-outrnaseq |
| spellingShingle | Zulfikar Azam Wei Shao Ho-keung Ng Jing Wang Zhong-ping Chen Shing-shun Tony To Comprehensive RNAseq analysis reveals PIK3CD promotes glioblastoma tumorigenesis by mediating PI3K-Akt signaling pathway Glioma glioblastoma integrin mesenchymal transformation phosphatidylinositol 3-kinase-akt phosphatidylinositol-4 5-bisphosphate 3-kinase catalytic subunit delta knock-out rnaseq |
| title | Comprehensive RNAseq analysis reveals PIK3CD promotes glioblastoma tumorigenesis by mediating PI3K-Akt signaling pathway |
| title_full | Comprehensive RNAseq analysis reveals PIK3CD promotes glioblastoma tumorigenesis by mediating PI3K-Akt signaling pathway |
| title_fullStr | Comprehensive RNAseq analysis reveals PIK3CD promotes glioblastoma tumorigenesis by mediating PI3K-Akt signaling pathway |
| title_full_unstemmed | Comprehensive RNAseq analysis reveals PIK3CD promotes glioblastoma tumorigenesis by mediating PI3K-Akt signaling pathway |
| title_short | Comprehensive RNAseq analysis reveals PIK3CD promotes glioblastoma tumorigenesis by mediating PI3K-Akt signaling pathway |
| title_sort | comprehensive rnaseq analysis reveals pik3cd promotes glioblastoma tumorigenesis by mediating pi3k akt signaling pathway |
| topic | glioblastoma integrin mesenchymal transformation phosphatidylinositol 3-kinase-akt phosphatidylinositol-4 5-bisphosphate 3-kinase catalytic subunit delta knock-out rnaseq |
| url | http://www.jglioma.com/article.asp?issn=2589-6113;year=2020;volume=3;issue=3;spage=135;epage=142;aulast= |
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