Abstract
Background/AimPrevious literature has implicated the sustained expression of FOXM1 in numerous human cancers, including head and neck squamous cell carcinoma (HNSCC). The current study aimed to elucidate the function and regulatory mechanism of FOXM1 in HNSCC.MethodsWestern blot and RT-qPCR methods were performed to evaluate the expression of Linc-ROR, FOXM1, and LMO4 in HNSCC tissue samples and cells. The binding between FOXM1 and Linc-ROR was analyzed using a ChIP assay. Various cellular processes including proliferation and invasion abilities were assessed following alteration of FOXM1, Linc-ROR and LMO4 expression in HNSCC cells. Xenograft mouse models were established to validate the in vitro findings.ResultsLinc-ROR and FOXM1 were highly expressed in HNSCC tissues and cells. FOXM1 operated as a potential transcription factor to bind to the promoter region of Linc-ROR. Linc-ROR and FOXM1 exhibited high expression levels in both the clinical tissue samples as well as the HNSCC cells, which could facilitate the proliferation and invasion of HNSCC cells. Linc-ROR upregulated the expression of LMO4 and promoted activation of the AKT/PI3K signaling pathway, thus stimulating the proliferation and invasion of HNSCC cells. Silencing of Linc-ROR brought about a contrasting effect relative to that seen when FOXM1 was overexpressed in HNSCC in vivo.ConclusionsOverall, FOXM1 promoted the expression of Linc-ROR and induced the activation of the LMO4-dependent AKT/PI3K signaling pathway, thus facilitating the occurrence and development of HNSCC.
Highlights
Head and neck squamous cell carcinoma (HNSCC) represents a malignancy encompassing a heterogeneous population of cancer cells that generally arise from the squamous epithelium of the oral cavity, oropharynx, larynx, as well as hypopharynx [1]
Linc-ROR and forkhead box M1 (FOXM1) were highly expressed in HNSCC tissues and cells
Silencing of Linc-ROR brought about a contrasting effect relative to that seen when FOXM1 was overexpressed in HNSCC in vivo
Summary
Head and neck squamous cell carcinoma (HNSCC) represents a malignancy encompassing a heterogeneous population of cancer cells that generally arise from the squamous epithelium of the oral cavity, oropharynx, larynx, as well as hypopharynx [1]. HPVpositive HNSCC is typically seen in young adults and nonsmokers [2]. HNSCC has been strongly associated with tobacco smoking [3]. Studies have indicated that the annual incidence of HNSCC is approximately 800,000 new cases globally [4]. In addition to surgical management [5], chemotherapy remains the first-line approach for advanced cases of HNSCC, with agents such as platinum combined with cetuximab, nivolumab or pembrolizumab often employed [6, 7]. Despite clinical success of the aforementioned modalities, the five-year survival rate remains unsatisfactory [8]
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