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Title:
PIK3R3, a regulatory subunit of PI3K, modulates ovarian cancer stem cells and ovarian cancer development and progression by integrative analysis | BMC Cancer
Description:
Background Ovarian cancer is the most lethal gynecologic disease and is one of the most commonly diagnosed cancers among women worldwide. The phosphatidylinositol 3-kinase (PI3K) family plays an important regulatory role in various cancer signaling pathways, including those involved in ovarian cancer development; however, its exact function remains to be fully understood. We conducted this study to understand the role of P13K in the molecular mechanisms underlying ovarian cancer development. Methods To determine the differential gene expression of phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3), a regulatory subunit of PI3K, in normal, tumor, and metastatic ovary tissues, TNM plotter analysis was performed. The microarray dataset GSE53759 was downloaded from Gene Expression Omnibus. ROC plotter analysis was conducted to understand the potential of PIK3R3 as a predictive marker for effectiveness of therapy in ovarian cancer. muTarget was used to identify mutations that alter PIK3R3 expression in ovarian cancer. To determine the interacting partners for PIK3R3 in ovarian tissues, the interactome-atlas tool was used. The Kyoto encyclopedia of genes and genomes (KEGG) analysis was conducted to identify the pathways in which these interacting partners were primarily enriched. Results PIK3R3 was overexpressed in ovarian and metastatic tumors. Elevated PIK3R3 levels were observed in ovarian cancer stem cells, wherein inhibiting PIK3R3 expression significantly reduced the size of ovarian cancer spheroids. Treatment of ovarian cancer stem cells with PF-04691502 (10 μM), an inhibitor of both PI3K and mTOR kinases, also reduced the size of spheroids and the level of OCT4. PIK3R3 was highly expressed in ovarian cancer with several somatic mutations and was predicted better outcomes in patients undergoing Avastin® chemotherapy using bioinformatic tool. Protein interaction analysis showed that PIK3R3 interacts with 157 genes, including GRB2, EGFR, ERBB3, PTK2, HCK, IGF1R, YES1, and PIK3CA, in the ovary. KEGG enrichment analysis revealed that the interacting partners of PIK3R3 are involved in the ErbB signaling pathway, proteoglycans in cancer, FoxO, prolactin, chemokine, and insulin signaling pathways. Conclusions PIK3R3 plays a pivotal role in ovarian cancer development and is therefore a potential candidate for developing novel therapeutic approaches.
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real-time quantitative reverse transcription pcr transcriptome-level open-access database org/ensg00000117461-pik3r3/pathology/ovarian+cancer phase ii trial ultra-low attachment plates eun jung sohn enables real-time comparison relapse-free survival time erb-b2 receptor tyrosine indispensable transcription factor triple-negative breast cancer ovarian cancer-initiating cells article google scholar isolate spheroid-forming cells gov/geo/query/acc hrp-conjugated secondary antibodies stem cell-related genes article download pdf modulating cell growth egf/erbb receptor family induces epithelial–mesenchymal transition cancer genome atlas [tcga] predicting progression-free survival identify molecular target pf-04691502 treated a2780-sp national research foundation bio-rad protein assay web-based david v6 pi3k/akt signaling pathway protein–protein interaction data cancer stem cells stem cancer cells p85 regulatory subunit ovarian carcinoma igrov-1 skov3-sp cells compared interactome-atlas tool showed enhances cell proliferation privacy choices/manage cookies receiver operating characteristic sirna-mediated pik3r3 knockdown epithelial ovarian cancer serous ovarian cancer stem cell properties pectrin beta chain serous ovarian carcinoma ovarian clear cancer ovarian cancer cells ovarian cancer development relapse-free survival ovarian cancer patients
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headline:PIK3R3, a regulatory subunit of PI3K, modulates ovarian cancer stem cells and ovarian cancer development and progression by integrative analysis
description:Ovarian cancer is the most lethal gynecologic disease and is one of the most commonly diagnosed cancers among women worldwide. The phosphatidylinositol 3-kinase (PI3K) family plays an important regulatory role in various cancer signaling pathways, including those involved in ovarian cancer development; however, its exact function remains to be fully understood. We conducted this study to understand the role of P13K in the molecular mechanisms underlying ovarian cancer development. To determine the differential gene expression of phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3), a regulatory subunit of PI3K, in normal, tumor, and metastatic ovary tissues, TNM plotter analysis was performed. The microarray dataset GSE53759 was downloaded from Gene Expression Omnibus. ROC plotter analysis was conducted to understand the potential of PIK3R3 as a predictive marker for effectiveness of therapy in ovarian cancer. muTarget was used to identify mutations that alter PIK3R3 expression in ovarian cancer. To determine the interacting partners for PIK3R3 in ovarian tissues, the interactome-atlas tool was used. The Kyoto encyclopedia of genes and genomes (KEGG) analysis was conducted to identify the pathways in which these interacting partners were primarily enriched. PIK3R3 was overexpressed in ovarian and metastatic tumors. Elevated PIK3R3 levels were observed in ovarian cancer stem cells, wherein inhibiting PIK3R3 expression significantly reduced the size of ovarian cancer spheroids. Treatment of ovarian cancer stem cells with PF-04691502 (10 μM), an inhibitor of both PI3K and mTOR kinases, also reduced the size of spheroids and the level of OCT4. PIK3R3 was highly expressed in ovarian cancer with several somatic mutations and was predicted better outcomes in patients undergoing Avastin® chemotherapy using bioinformatic tool. Protein interaction analysis showed that PIK3R3 interacts with 157 genes, including GRB2, EGFR, ERBB3, PTK2, HCK, IGF1R, YES1, and PIK3CA, in the ovary. KEGG enrichment analysis revealed that the interacting partners of PIK3R3 are involved in the ErbB signaling pathway, proteoglycans in cancer, FoxO, prolactin, chemokine, and insulin signaling pathways. PIK3R3 plays a pivotal role in ovarian cancer development and is therefore a potential candidate for developing novel therapeutic approaches.
datePublished:2022-06-27T00:00:00Z
dateModified:2022-06-27T00:00:00Z
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keywords:
Ovarian cancer
Cancer stem cells
Phosphatidylinositol 3-kinase
Phosphoinositide-3-kinase regulatory subunit 3
Cancer Research
Oncology
Surgical Oncology
Health Promotion and Disease Prevention
Biomedicine
general
Medicine/Public Health
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headline:PIK3R3, a regulatory subunit of PI3K, modulates ovarian cancer stem cells and ovarian cancer development and progression by integrative analysis
description:Ovarian cancer is the most lethal gynecologic disease and is one of the most commonly diagnosed cancers among women worldwide. The phosphatidylinositol 3-kinase (PI3K) family plays an important regulatory role in various cancer signaling pathways, including those involved in ovarian cancer development; however, its exact function remains to be fully understood. We conducted this study to understand the role of P13K in the molecular mechanisms underlying ovarian cancer development. To determine the differential gene expression of phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3), a regulatory subunit of PI3K, in normal, tumor, and metastatic ovary tissues, TNM plotter analysis was performed. The microarray dataset GSE53759 was downloaded from Gene Expression Omnibus. ROC plotter analysis was conducted to understand the potential of PIK3R3 as a predictive marker for effectiveness of therapy in ovarian cancer. muTarget was used to identify mutations that alter PIK3R3 expression in ovarian cancer. To determine the interacting partners for PIK3R3 in ovarian tissues, the interactome-atlas tool was used. The Kyoto encyclopedia of genes and genomes (KEGG) analysis was conducted to identify the pathways in which these interacting partners were primarily enriched. PIK3R3 was overexpressed in ovarian and metastatic tumors. Elevated PIK3R3 levels were observed in ovarian cancer stem cells, wherein inhibiting PIK3R3 expression significantly reduced the size of ovarian cancer spheroids. Treatment of ovarian cancer stem cells with PF-04691502 (10 μM), an inhibitor of both PI3K and mTOR kinases, also reduced the size of spheroids and the level of OCT4. PIK3R3 was highly expressed in ovarian cancer with several somatic mutations and was predicted better outcomes in patients undergoing Avastin® chemotherapy using bioinformatic tool. Protein interaction analysis showed that PIK3R3 interacts with 157 genes, including GRB2, EGFR, ERBB3, PTK2, HCK, IGF1R, YES1, and PIK3CA, in the ovary. KEGG enrichment analysis revealed that the interacting partners of PIK3R3 are involved in the ErbB signaling pathway, proteoglycans in cancer, FoxO, prolactin, chemokine, and insulin signaling pathways. PIK3R3 plays a pivotal role in ovarian cancer development and is therefore a potential candidate for developing novel therapeutic approaches.
datePublished:2022-06-27T00:00:00Z
dateModified:2022-06-27T00:00:00Z
pageStart:1
pageEnd:13
license:http://creativecommons.org/publicdomain/zero/1.0/
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keywords:
Ovarian cancer
Cancer stem cells
Phosphatidylinositol 3-kinase
Phosphoinositide-3-kinase regulatory subunit 3
Cancer Research
Oncology
Surgical Oncology
Health Promotion and Disease Prevention
Biomedicine
general
Medicine/Public Health
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