Abstract
Oral squamous cell carcinoma (OSCC) is one of the major leading causes of cancer-related death worldwide, with limited effective markers for diagnosis and therapy, which has caused a low overall survival rate in the past decades. Kinases play important roles in tumor development and malignancy in various types of cancer. However, little is known about the role of kinases in OSCC cells. In this study, an arrayed kinome small interfering RNA (siRNA) library was used to screen oral cancer cell lines and counter assayed with normal fibroblast cells to identify the genes required for cancer cell proliferation. We found that polo-like kinase 1 (PLK1) was one of the most potent genes required for OSCC cell proliferation. The knockdown of PLK1 with a siRNA or antisense oligonucleotide (ASO) consistently diminished cyclin-B1 (CCNB1) expression/phosphorylation and the G2-M phase transition. Similar effects were observed in cells treated with the PLK1 kinase inhibitor BI6727. Besides, The Cancer Genome Atlas (TCGA) analysis revealed that PLK1 was elevated in tumor tissues and associated with short survival in patients with OSCC. We also found that PLK1 expression was highly correlated with the expression of its downstream effector, CCNB1, in patients with OSCC. Coexpression of the two genes resulted in a poor prognosis of OSCC patients, particularly those in the advanced stages of OSCC. Taken together, our results suggest that PLK1 might be a diagnostic or therapeutic marker for OSCC.
Highlights
Oral squamous cell carcinoma (OSCC) is one of the major leading causes of cancer death worldwide, with increasing incidence, in South Asia [1]
We further evaluated the expression of candidate genes in OSCC patients with the The Cancer Genome Atlas (TCGA) dataset, which consists of corresponding normal tissues from patients, primary tumors (n = 315), and metastatic tumors (n = 2) (Figure 1E)
High polo-like kinase 1 (PLK1) expression was associated with worse overall survival in OSCC patients with certain demographical and pathological features
Summary
Oral squamous cell carcinoma (OSCC) is one of the major leading causes of cancer death worldwide, with increasing incidence, in South Asia [1]. Cancers 2019, 11, 1117 in South Asia, smoking and alcohol consumption are the most common risk factors for OSCC development. Surgery and postoperative radiation therapy are standard procedures for OSCC treatment. Growing studies have shown that several prognostic factors are associated with poor survival or relapse [2]. None of the prognostic factors have been proven to be a suitable target for OSCC. The 5-year overall survival rate has not significantly improved in the last decade, which supports the urgent requirement for suitable therapeutic biomarkers or targets for OSCC
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