Overexpression of cyclin D1 in meningioma is associated with malignancy grade and causes abnormalities in apoptosis, invasion and cell cycle progression

Abstract

Cyclin D1 has been reported overexpressed in many malignant cancers. However, the expression pattern and biological function of cyclin D1 in meningiomas are still unknown. In this study, we examined the expression of cyclin D1 in meningioma with immunohistochemistry and correlated the measure to the recurrence. Potential effects of cyclin D1 on tumor growth and apoptosis were also examined in representative cell lines (IOMM-Lee and CH157) by inhibiting cyclin D1 with RNA interference. We demonstrate that cyclin D1 mRNA and protein expression are positively correlated with meningioma grade and that higher cyclin D1 expression correlates with higher recurrence. Knockdown of cyclin D1 by the siRNA decreased IOMM-Lee and CH157 cell proliferation, promoted the rate of apoptosis and attenuated invasive capacity. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot analysis revealed that cells stably underexpressing cyclin D1 showed lower expression of survivin and the antiapoptotic protein B cell lymphoma-2 (Bcl-2) compared to control cells. These results indicate that high cyclin D1 expression is associated with a poor outcome of meningioma patients and knockdown of cyclin D1 expression may be a potential treatment for malignant meningioma.

Anaplastic and meningothelial meningiomas in a single tumor: A “dedifferentiated meningioma”?

“…The immunohistochemical expression of cyclin D1 in meningioma has been investigated by some authors, and Cheng et al . demonstrated markedly higher expression in atypical and anaplastic meningiomas . Milenković et al .…”

“…The loss of nuclear expression associated with the acquisition of cytoplasmic immunoreactivity for cyclin D1 in the anaplastic component is an interesting finding in our case. Cyclin D1 is a check‐point protein located in the nucleus which is involved in the progression of cells through the G1 phase of the cell cycle, and its expression is increased in actively proliferating neoplasms, including some dedifferentiated neoplasms . The immunohistochemical expression of cyclin D1 in meningioma has been investigated by some authors, and Cheng et al .…”

“…Cyclin D1 is a check-point protein located in the nucleus which is involved in the progression of cells through the G1 phase of the cell cycle, and its expression is increased in actively proliferating neoplasms, including some dedifferentiated neoplasms. 13,28 The immunohistochemical expression of cyclin D1 in meningioma has been investigated by some authors, [28][29][30][31] and Cheng et al demonstrated markedly higher expression in atypical and anaplastic meningiomas. 28 Milenković et al 30 and Ahmad et al 31 documented the cytoplasmic translocation of cyclin D1 in menigioma.…”

“…13,28 The immunohistochemical expression of cyclin D1 in meningioma has been investigated by some authors, [28][29][30][31] and Cheng et al demonstrated markedly higher expression in atypical and anaplastic meningiomas. 28 Milenković et al 30 and Ahmad et al 31 documented the cytoplasmic translocation of cyclin D1 in menigioma. Although they found no significant correlation between this finding and the tumor grade or patients' survival, 30,31 this finding probably indicates the dedifferentiation of meningioma cells.…”

Analysis of Minichromosome Maintenance-2 (MCM-2) and Cyclin D1 Expression in Meningioma

“…Overexpression of Cyclin D1 has been associated with shorter G1 phase and abnormal cell proliferation. This has been reported in many malignant tumors (Moraes et al 2012, Cheng et al 2015. The aim of this study was to analyze the differences and correlation between MCM-2 and Cyclin D1 in various meningioma gradings.…”