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PHF20 inhibition promotes apoptosis and cisplatin chemosensitivity via the OCT4‑p‑STAT3‑MCL1 signaling pathway in hypopharyngeal squamous cell carcinoma.

ABSTRACT: Cisplatin is a widely used platinum‑based chemotherapeutic agent for hypopharyngeal squamous cell carcinoma (HSCC). However, resistance to cisplatin limits its use for the treatment of HSCC, and the underlying molecular mechanism requires further investigation. The present study performed functional assays to determine whether the expression of plant homeodomain finger protein 20 (PHF20) may be involved in the apoptosis and cisplatin resistance of HSCC. The expression levels of PHF20 were higher in cisplatin‑resistant HSCC cells compared with those in cisplatin‑sensitive cells. The inhibition of PHF20 suppressed cell viability but did not affect the migratory and invasive abilities of HSCC cells compared with those of negative control‑transfected cells. Furthermore, PHF20 inhibition reduced cell viability by enhancing apoptosis compared with those in the control cells in vitro. Notably, the inhibition of PHF20 sensitized HSCC cells to cisplatin, thus increasing apoptosis via the signal transducer and activator of transcription 3 (STAT3)‑myeloid cell leukemia‑1 (MCL1) pathway. Octamer‑binding transcription factor 4 (OCT4) overexpression restored phosphorylated STAT3‑MCL1‑mediated apoptosis induced by PHF20 inhibition. In vivo experiments confirmed that PHF20 silencing induced tumor growth and increased apoptosis in HSCC cells compared with those in the control cells. Thus, PHF20 inhibition may promote apoptosis and improve cisplatin chemosensitivity via the OCT4‑p‑STAT3‑MCL1 signaling pathway in HSCC.

SUBMITTER: Liu X

PROVIDER: S-EPMC8121096 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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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PHF20 inhibition promotes apoptosis and cisplatin chemosensitivity via the OCT4‑p‑STAT3‑MCL1 signaling pathway in hypopharyngeal squamous cell carcinoma.

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