Dataset Information

FOXM1a Isoform of Oncogene FOXM1 Is a Tumor Suppressor Suppressed by hnRNP C in Oral Squamous Cell Carcinoma.

ABSTRACT: FOXM1 is an oncogenic transcriptional factor and includes several isoforms generated by alternative splicing. Inclusion of alternative exon 9 produces FOXM1a, a transcriptionally inactive isoform. However, the role of FOXM1a in tumorigenesis remains unknown. In addition, the regulatory mechanisms of exon 9 splicing are also unclear. In the present study, we found that overexpression of FOXM1a significantly reduced cell proliferation and colony formation of oral squamous cell carcinoma (OSCC) cell proliferation in vitro. Importantly, OSCC cells with FOXM1a overexpression showed significantly slower tumor formation in nude mice. Moreover, we identified a U-rich exonic splicing suppressor (ESS) which is responsible for exon 9 skipping. Splicing factor heterogeneous nuclear ribonucleoprotein C (hnRNP C) can bind to the ESS and suppress exon 9 inclusion and FOXM1a expression. Silence of hnRNP C also significantly suppresses OSCC cell proliferation. HnRNP C is significantly co-expressed with FOXM1 in cancers. Our study uncovered a novel regulatory mechanism of oncogene FOXM1 expression in OSCC.

SUBMITTER: Jia R

PROVIDER: S-EPMC10526205 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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FOXM1a Isoform of Oncogene FOXM1 Is a Tumor Suppressor Suppressed by hnRNP C in Oral Squamous Cell Carcinoma.

Jia Rong R Che Xiaoxuan X Jia Jun J Guo Jihua J

Biomolecules 20230830 9

FOXM1 is an oncogenic transcriptional factor and includes several isoforms generated by alternative splicing. Inclusion of alternative exon 9 produces FOXM1a, a transcriptionally inactive isoform. However, the role of FOXM1a in tumorigenesis remains unknown. In addition, the regulatory mechanisms of exon 9 splicing are also unclear. In the present study, we found that overexpression of FOXM1a significantly reduced cell proliferation and colony formation of oral squamous cell carcinoma (OSCC) cel ...[more]

PMID: 37759731

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Project description:BackgroundOral squamous cell carcinoma (OSCC) is a genetic and epigenetic disease. There is growing evidence to suggest that environmental factors due to epigenetic changes can be involved in the OSCC pathogenesis. Although tumor suppressor genes (TSGs) are commonly inactivated by promoter hypermethylation in human cancers, the epigenetic changes and the mechanism of TSGs in human OSCC remain unclear. We therefore assessed the methylation status of the TSGs, which are associated with epigenetic silencing in human cancers, OSCC cell lines, primary tumors, and normal oral mucosa.ResultsWe used 14 TSGs that were originally identified in colon cancer to investigate the aberrant hypermethylation of these genes associated with transcriptional silencing in 10 OSCC cell lines. We found three TSGs, TFPI2, SOX17, and GATA4, that are robustly hypermethylated and are associated with transcriptional silencing in OSCC cell lines. The re-expression of the three genes was induced by 5-aza-2'-deoxycytidine (5-aza-dC) in cells in which these genes were not expressed or had a lack of expression. In 33 cases of primary OSCC tumors, promoter hypermethylation was detected for the TFPI2, SOX17, and GATA4 genes at (32/33) 97%, (22/33) 67%, and (11/33) 33%, respectively. Eleven normal oral mucosa samples showed no promoter hypermethylation for all three genes, which suggests that this promoter hypermethylation is cancer-specific. Bisulfite sequencing analysis confirmed the cancer-specific methylation of the TFPI2, SOX17, and GATA4 promoters in the OSCC cell lines and tumors but not in the normal oral mucosa samples. More importantly, the methylation status of TFPI2, GATA4, and SOX17 was significantly associated with OSCC patients' overall survival through TCGA DNA methylation database.ConclusionsWe identified that TFPI2, SOX17, and GATA4 are frequently hypermethylated in human OSCC cells in a cancer-specific manner and that the transcriptional expression of these genes is regulated by promoter hypermethylation in OSCC. Our results highlight the great potential used as a synergistic biomarker set to improve the prognosis and therapeutic treatment for patients with OSCC.

Dataset Information

FOXM1a Isoform of Oncogene FOXM1 Is a Tumor Suppressor Suppressed by hnRNP C in Oral Squamous Cell Carcinoma.

Publications

FOXM1a Isoform of Oncogene FOXM1 Is a Tumor Suppressor Suppressed by hnRNP C in Oral Squamous Cell Carcinoma.

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