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Pparg may Promote Chemosensitivity of Hypopharyngeal Squamous Cell Carcinoma.

ABSTRACT: The upregulation of peroxisome proliferator-activated receptor gamma (PPARG) has been shown to increase the chemosensitivity of several human cancers. This study is aimed at studying if PPARG sensitizes hypopharyngeal squamous cell carcinoma (HSCC) in chemotherapeutic treatments and at dissecting possible mechanisms of observed effects. We integrated large-scale literature data and HSCC gene expression data to identify regulatory pathways that link PPARG and chemosensitivity in HSCC. Expression levels of molecules within the PPARG regulatory pathways were compared in 21 patients that underwent chemotherapy for primary HSCC, including 12 chemotherapy-sensitive patients (CSP) and 9 chemotherapy-nonsensitive patients (CNSP). In the CPS group, expression levels of PPARG were higher than that in the CNSP group (log-fold-change = 0.50). Structured text mining identified two chemosensitivity-related regulatory pathways driven by PPARG. In the CSP group, expression levels for 7 chemosensitivity-promoting genes were increased, while for 13 chemosensitivity suppressing the gene expression levels were decreased. Our results support the chemosensitivity-promoting role of PPARG in HSCC tumor cells, most likely by affecting both cell proliferation and cell motility pathways.

SUBMITTER: Lian M

PROVIDER: S-EPMC7193298 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Pparg may Promote Chemosensitivity of Hypopharyngeal Squamous Cell Carcinoma.

Lian Meng M Chen Jiaming J Shen Xixi X Hou Lizhen L Fang Jugao J

PPAR research 20200422

The upregulation of peroxisome proliferator-activated receptor gamma (PPARG) has been shown to increase the chemosensitivity of several human cancers. This study is aimed at studying if PPARG sensitizes hypopharyngeal squamous cell carcinoma (HSCC) in chemotherapeutic treatments and at dissecting possible mechanisms of observed effects. We integrated large-scale literature data and HSCC gene expression data to identify regulatory pathways that link PPARG and chemosensitivity ...[more]

PMID: 32373170

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Project description:OBJECTIVE: To investigate the differentially expressed genes and miRNAs related to the chemosensitivity of hypopharyngeal squamous cell carcinoma ï¼HSCCï¼by microarrays and miRNA arrays. METHODS: 1. A total number of 21 patients who underwent induction chemotherapy for primary hypopharyngeal squamous cell carcinoma (12 patients are sensitive to chemotherapy ,and others are not) were recruited for microarray and miRNA array gene expression analysis 2. Bioinformatics analysis of differentially expressed genes screened by microarrays : The differential gene cluster analysis was applied in biological processes, cellular components and molecular functions by GO database; The differential gene enrichment analysis was applied in signaling pathways by KEGG database, and the differentially expressed and biologically meaningful core genes would be screened. 3. Prediction and analysis of target genes of differentially expressed miRNAs: TargetScan, PITA and microRNAorg methods were used for target gene prediction in GeneSpring 12.5 software, and the intersection of the three methods analysis was considered as significant target genes. Considering the result of microarrays, the intersection of the predicted target genes and the genes screened by microarrays would be analyzed by bioinformatics, which were considered as genes regulated by different miRNAs. RESULTS: 1. Analyzed by microarrays, there were 1579 genes significantly related to the sensitivity to chemotherapy; Among these 1579genes, 815 showed a higher expression in the tissue from patients who are sensitive to chemotherapy , while 764 presented the contrasting pattern. 2. Analyzed by miRNA arrays, there were 24 genes significantly related to the sensitivity to chemotherapy; Among them, 6 showed a higher expression in the tissue from patients who are sensitive to chemotherapy , while 18 presented the contrasting pattern. TargetScan, PITA and microRNAorg were used for target gene prediction in GeneSpring 12.5 software, and the intersection of the three methods analysis was considered as significant target genes. There were 613 putative target genes corresponding to the 24 significant miRNAs. Among them, six genes(MAPK14, ADCY1, GSTM4, CDC42, JUN, GPX6) were statistically and biologically different related to the sensitivity to chemotherapy. And among the 24 significant miRNAs, miR-193b-3pãmiR-211-3pãmiR-4253ãmiR-4496ãmiR-6738-5p could regulate them. CONCLUSIONS: The research revealed a gene expression signature of chemosensitivity in hypopharyngeal squamous cell carcinoma by microarrays and miRNA arrays. The result will contribute to the understanding of the molecular basis of hypopharyngeal squamous cell carcinoma and help to improve diagnosis and treatment. 1. A total number of 21 patients who underwent induction chemotherapy for primary hypopharyngeal squamous cell carcinoma (12 patients are sensitive to chemotherapy ,and others are not) were recruited for microarray and miRNA array gene expression analysis 2. Bioinformatics analysis of differentially expressed genes screened by microarrays : The differential gene cluster analysis was applied in biological processes, cellular components and molecular functions by GO database; The differential gene enrichment analysis was applied in signaling pathways by KEGG database, and the differentially expressed and biologically meaningful core genes would be screened. 3. Prediction and analysis of target genes of differentially expressed miRNAs: TargetScan, PITA and microRNAorg methods were used for target gene prediction in GeneSpring 12.5 software, and the intersection of the three methods analysis was considered as significant target genes. Considering the result of microarrays, the intersection of the predicted target genes and the genes screened by microarrays would be analyzed by bioinformatics, which were considered as genes regulated by different miRNAs.

Project description:OBJECTIVE: To investigate the differentially expressed genes and miRNAs related to the chemosensitivity of hypopharyngeal squamous cell carcinoma （HSCC）by microarrays and miRNA arrays. METHODS: 1. A total number of 21 patients who underwent induction chemotherapy for primary hypopharyngeal squamous cell carcinoma (12 patients are sensitive to chemotherapy ,and others are not) were recruited for microarray and miRNA array gene expression analysis 2. Bioinformatics analysis of differentially expressed genes screened by microarrays : The differential gene cluster analysis was applied in biological processes, cellular components and molecular functions by GO database; The differential gene enrichment analysis was applied in signaling pathways by KEGG database, and the differentially expressed and biologically meaningful core genes would be screened. 3. Prediction and analysis of target genes of differentially expressed miRNAs: TargetScan, PITA and microRNAorg methods were used for target gene prediction in GeneSpring 12.5 software, and the intersection of the three methods analysis was considered as significant target genes. Considering the result of microarrays, the intersection of the predicted target genes and the genes screened by microarrays would be analyzed by bioinformatics, which were considered as genes regulated by different miRNAs. RESULTS: 1. Analyzed by microarrays, there were 1579 genes significantly related to the sensitivity to chemotherapy; Among these 1579genes, 815 showed a higher expression in the tissue from patients who are sensitive to chemotherapy , while 764 presented the contrasting pattern. 2. Analyzed by miRNA arrays, there were 24 genes significantly related to the sensitivity to chemotherapy; Among them, 6 showed a higher expression in the tissue from patients who are sensitive to chemotherapy , while 18 presented the contrasting pattern. TargetScan, PITA and microRNAorg were used for target gene prediction in GeneSpring 12.5 software, and the intersection of the three methods analysis was considered as significant target genes. There were 613 putative target genes corresponding to the 24 significant miRNAs. Among them, six genes(MAPK14, ADCY1, GSTM4, CDC42, JUN, GPX6) were statistically and biologically different related to the sensitivity to chemotherapy. And among the 24 significant miRNAs, miR-193b-3p、miR-211-3p、miR-4253、miR-4496、miR-6738-5p could regulate them. CONCLUSIONS: The research revealed a gene expression signature of chemosensitivity in hypopharyngeal squamous cell carcinoma by microarrays and miRNA arrays. The result will contribute to the understanding of the molecular basis of hypopharyngeal squamous cell carcinoma and help to improve diagnosis and treatment.

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Pparg may Promote Chemosensitivity of Hypopharyngeal Squamous Cell Carcinoma.

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<i>Pparg</i> may Promote Chemosensitivity of Hypopharyngeal Squamous Cell Carcinoma.

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