Abstract
ORAL squamous cell carcinoma (OSCC) is a malignant tumor with the highest incidence among tumors involving the oral cavity maxillofacial region, and is notorious for its high recurrence and metastasis potential. Long non-coding RNAs (lncRNAs), which regulate the genesis and evolution of cancers, are potential prognostic biomarkers. This study identified HOTAIRM1 as a novel significantly upregulated lncRNA in OSCC, which is strongly associated with unfavorable prognosis of OSCC. Systematic bioinformatics analyses demonstrated that HOTAIRM1 was closely related to tumor stage, overall survival, genome instability, the tumor cell stemness, the tumor microenvironment, and immunocyte infiltration. Using biological function prediction methods, including Weighted gene co-expression network analysis (WGCNA), Gene set enrichment analysis (GSEA), and Gene set variation analysis (GSVA), HOTAIRM1 plays a pivotal role in OSCC cell proliferation, and is mainly involved in the regulation of the cell cycle. In vitro, cell loss-functional experiments confirmed that HOTAIRM1 knockdown significantly inhibited the proliferation of OSCC cells, and arrested the cell cycle in G1 phase. At the molecular level, PCNA and CyclinD1 were obviously reduced after HOTAIRM1 knockdown. The expression of p53 and p21 was upregulated while CDK4 and CDK6 expression was decreased by HOTAIRM1 knockdown. In vivo, knocking down HOTAIRM1 significantly inhibited tumor growth, including the tumor size, weight, volume, angiogenesis, and hardness, monitored by ultrasonic imaging and magnetic resonance imaging In summary, our study reports that HOTAIRM1 is closely associated with tumorigenesis of OSCC and promotes cell proliferation by regulating cell cycle. HOTAIRM1 could be a potential prognostic biomarker and a therapeutic target for OSCC.
Highlights
Oral squamous cell carcinoma (OSCC) is recognized for its high recurrence and metastasis rate, and is the most frequent malignancy in oral tumors, and in particular, presents constantly increasing morbidity (Ferlay et al, 2015; Economopoulou et al, 2017)
The data used for our analysis was obtained from TCGA-head and neck squamous carcinoma (HNSC) dataset, which can be downloaded through the Genomic Data Commons (GDC), and including the following information: Exp (expression data gathered in HTSeq-Counts, HTSeq-FPKM, copy number variation (CNV) and somatic mutations data
Among the DEGs, HOTAIRM1 was observed to be a markedly upregulated Long non-coding RNAs (lncRNAs), which has not been reported in previous studies on OSCC
Summary
Oral squamous cell carcinoma (OSCC) is recognized for its high recurrence and metastasis rate, and is the most frequent malignancy in oral tumors, and in particular, presents constantly increasing morbidity (Ferlay et al, 2015; Economopoulou et al, 2017). Surgeons are constantly adjusting surgical approaches and improving multidisciplinary therapy, the 5-years survival rate of 50% still represents a very poor prognosis, which is related to the specific tissue involved, clinical features, histopathological grading, or other factors (Bray et al, 2018). From another standpoint, the cure rate increases to above 90% through early interventional treatment, in individuals who are diagnosed with early-stage cancer (Lingen et al, 2008; Qiu et al, 2021a). The expression pattern and molecular function of HOTAIRM1 in OSCC have not been elucidated to date
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