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Genome-wide enhancer analysis reveals the role of AP-1 transcription factor in head and neck squamous cell carcinoma [RNA-Seq]

ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of human cancer. It causes significant morbidity and mortality, with a low 5-year survival rate. we used RNA-Seq to analyze the tumor and normal tissues of the head of the Tgfbr1/Pten 2cKO mouse model. RNA-Seq analysis found enhanced keratinization, cell proliferation, angiogenesis, inflammation and immune response, TNF signaling pathway, NF-kappa B signaling pathway, and p53 signaling pathway in tumor tissues，which ultimately contribute to HNSCC progression.

ORGANISM(S): Mus musculus

PROVIDER: GSE172322 | GEO | 2021/07/30

REPOSITORIES: GEO

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Project description:Distant metastasis is a major factor associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC), but little is known of its molecular mechanisms. New markers that predict clinical outcome, in particular the ability of primary tumors to develop metastatic tumors, are urgently needed. Here, we identified neurotensin, highly expressed in HNSCCs in comparison with normal tissues, as an invasion-promoting factor in HNSCC by using microarray analysis of clinical samples. Indeed, neurotensin overexpression associated with lymph node metastasis of neck, and tumors exhibiting neurotensin overexpression had a poor distant metastasis-free survival rate. In HNSCC cells which expressed neurotensin receptor 1 (NTSR1), neurotensin promoted cellular invasion, migration, and induction of matrix metalloproteinases transcripts. Disruption of NTSR1 signaling by silencing RNA caused the reversion of the invasion of HNSCC cells. By further microarray analysis using neurotensin-treated cells, neurotensin caused increased expression of genes implicated in tumor progression and metastasis including cell growth, migration, invasion, adhesion, angiogenesis, and apoptosis. Our findings have revealed a critical role of neurotensin/NTSR1 for invasion and migration in the metastatic process of HNSCC. This study raises the possibility that neurotensin/NTSR1 could be used as a possible predictive marker and a molecular therapeutic target in the antimetastatic strategies of HNSCC. Keywords: Identification of a novel therapeutic target for head and neck squamous cell carcinomas A total of 21 primary HNSCC samples were obtained from patients who underwent tumor resection at Chiba University Hospital (Chiba, Japan). 21 samples of normal-appearing mucosa at the margin of the surgical resection several centimeters from the tumor were also collected and designated histologically normal mucosa. 21 HNSCCs and paired normal tissues were used for microarray experiment. The clinicopathological grade was classified according to the criteria of the Japan Society for Head and Neck Cancer. The Ethics Committee of Chiba University approved our study, and informed consent was obtained from all patients for use of their tissue samples and clinical data. Tissue samples were immediately snap frozen in liquid nitrogen and stored at -80Â°C until use.

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Genome-wide enhancer analysis reveals the role of AP-1 transcription factor in head and neck squamous cell carcinoma [RNA-Seq]

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