Abstract
BubR1 is a critical component of spindle assembly checkpoint, ensuring proper chromatin segregation during mitosis. Recent studies showed that BubR1 was overexpressed in many cancer cells, including oral squamous cell carcinomas (OSCC). However, the effect of BubR1 on metastasis of OSCC remains unclear. This study aimed to unravel the role of BubR1 in the progression of OSCC and confirm the expression of BubR1 in a panel of malignant OSCC cell lines with different invasive abilities. The results of quantitative real-time PCR showed that the mRNA level of BubR1 was markedly increased in four OSCC cell lines, Ca9-22, HSC3, SCC9 and Cal-27 cells, compared to two normal cells, normal human oral keratinocytes (HOK) and human gingival fibroblasts (HGF). Moreover, the expression of BubR1 in these four OSCC cell lines was positively correlated with their motility. Immunofluorescence revealed that BubR1 was mostly localized in the cytosol of human gingival carcinoma Ca9-22 cells. BubR1 knockdown significantly decreased cellular invasion but slightly affect cellular proliferation on both Ca9-22 and Cal-27 cells. Consistently, the activities of metastasis-associated metalloproteinases MMP-2 and MMP-9 were attenuated in BubR1 knockdown Ca9-22 cells, suggesting the role of BubR1 in promotion of OSCC migration. Our present study defines an alternative pathway in promoting metastasis of OSCC cells, and the expression of BubR1 could be a prognostic index in OSCC patients.
Highlights
Death due to head and neck cancer has been on the rise in recent decades, accounting for around580,000 cancer-related deaths worldwide in 2013 [1]
To confirm the relevance about promotion to a malignant state of oral squamous cell carcinomas (OSCC) could be accelerated by increasing of BubR1 levels, real-time PCR analyses were performed to investigate the mRNA levels of BubR1 in five OSCC cell lines, all of which have differential carcinomatous state with confirmed invasive ability, compared to normal primary human oral keratinocytes (HOK) and human normal gingival fibroblasts (HGF)
This BubR1 levels in those of tested OSCC cell lines were quite consistent with their respective ability of cellular invasion that had been examined previously by using transwell assays [17]
Summary
Death due to head and neck cancer has been on the rise in recent decades, accounting for around. MMP-2 and MMP-9, the two zinc-dependent endopeptidases with collagenase and gelatinase activity, have been reported to have high expression at the invasive front of OSCC tumor [6]. It is often asymptomatic at early stages, the appearance of neck lymph node metastasis seems to be a prognostic determinant for patients with OSCC [7]. There are many available effective screening methods for neck metastasis, such as computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) They are not enough to accurately diagnose the metastasis in cervical lymph nodes [8]. The effects of BubR1 on metastasis-related hallmarks, including the activity of MMP-2 and MMP-9, were examined and discussed
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