Abstract
The aim of this study was to observe the regulatory action of the polo-like kinase 1 (PLK1) gene in the invasion of anaplastic thyroid carcinoma cells and investigate its mechanisms. The expression of the PLK1 protein in 36 patients with anaplastic thyroid carcinoma was detected by immunohistochemical staining. siRNA against PLK1 was designed, synthesized and transfected into ARO cells. The effects of PLK1 siRNA on cell invasion were detected by a soft agar colony formation assay and a Transwell chamber assay. The corresponding protein was detected using western blot analysis. The expression of PLK1 in anaplastic thyroid carcinoma samples (67.5±10.6%) was significantly higher compared to that in cancer-adjacent samples (0.65%±0.12%; P<0.01). The expression of PLK1 correlated with clinical stage, lymph node metastasis and prognosis of anaplastic thyroid. The number of cell clones was reduced in a dose-dependent manner with increasing levels of siRNA and the number of cells permeating through the filter membrane decreased following transfection with siRNA. The inhibition of PLK1 caused a significant decrease in CD44v6, matrix metalloproteinase (MMP)-2 and MMP-9 (0.36±0.08, 0.12±0.03, 0.25±0.06, respectively) compared to the non-transfected group (1.15±0.18, 1.21±0.20, 1.25±0.21, respectively; P<0.01). In conclusion, the expression of PLK1 was found to be increased in anaplastic thyroid carcinoma and was correlated with clinical stage, lymph node metastasis and prognosis. Additionaly, PLK1 siRNA was found to inhibit the invasion of anaplastic thyroid carcinoma cells. Therefore, CD44v6, MMP-2 and MMP-9 are likely to be involved in the regulation of cell invasion induced by PLK1.
Highlights
Polo-like kinase 1 (PLK1) is a highly conserved serine/ threonine kinase that plays an important role in mitosis [1]
It has been demonstrated that the PLK1 gene plays an important role in the incidence and development of tumors
PLK1 expression is upregulated in a number of tumors including esophageal carcinoma [4,5], multiple myeloma [6], gynecological malignant tumors [7], skin cancer [8], liver cancer [9], gastric carcinoma [10] and cervical cancer [11]
Summary
Polo-like kinase 1 (PLK1) is a highly conserved serine/ threonine kinase that plays an important role in mitosis [1]. PLK1 is highly expressed in numerous tumor tissues or cells and is associated with clinical stage, metastasis and invasiveness, as well as with the prognosis of patients with tumors. There is no curative regimen for undifferentiated thyroid carcinoma, which is highly malignant and progresses rapidly. The PLK1 gene is known to play an important regulatory role in the cell proliferation of undifferentiated thyroid carcinoma. The association between PLK1 and thyroid carcinoma cell invasiveness has yet to be adequately investigated. We first examined the relationship among PLK1 expression and clinical stage and lymphatic metastasis in undifferentiated thyroid carcinoma tissue. The effect of PLK1 RNAi on the invasiveness of undifferentiated thyroid carcinoma ARO cells was investigated. We explored the possible mechanism behind CD44v6/matrix metalloproteinase (MMP)-2/MMP-9
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