The expression of SIRT1 regulates the metastaticplasticity of chondrosarcoma cells by inducing epithelial-mesenchymal transition

Abstract

SIRT1 belongs to the mammalian sirtuin family and plays an important role in deacetylating histone and nonhistone proteins. It is reported that SIRT1 is associated with tumor metastasis in several kinds of tumors. However, the effect of SIRT1 on the metastasis of chondrosarcoma cells is still unknown. In this study, we demonstrated that up and down-regulation of SIRT1 expression could significantly change the invasive and metastatic potential in chondrosarcoma cell line. Besides that, the result from the nude mice confirmed the effect of SIRT1 on metastasis of chondrosarcoma cells. Furthermore, we also found that SIRT1 effectively enhanced the metastasis by inducing epithelial-mesenchymal transition (EMT) in chondrosarcoma cells. Inhibition the expression of SIRT1 could block the incidence of metastasis and EMT in chondrosarcoma cells. In addition, we also observed that SIRT1 could enhance the expression of Twist which is a key transcriptional factor of EMT. A clinicopathological analysis showed that SIRT1 expression was significantly correlated with the poor prognosis of pelvis chondrosarcoma. Kaplan-Meier survival curves revealed that positive SIRT1 expression was associated with poor prognosis in patients with pelvis chondrosarcoma. Taken together, these results indicate that SIRT1 may promote the metastasis of chondrosarcoma by inducing EMT and can be a potential molecular target for chondrosarcoma therapy.

Identification of significant gene biomarkers of low back pain caused by changes in the osmotic pressure of nucleus pulposus cells

“…The expression of GAPDH was measured as an internal control. Thermocycler conditions included an initial hold at 50 °C for 2 minutes and then 95 °C for 10 minutes followed by a two-step PCR programme of 95 °C for 15 seconds and 60 °C for 60 seconds repeated for 40 cycles on an Mx4000 system (Applied Biosystems, Foster City, CA), on which data were collected and quantitatively analysed 79 . The expression level of mRNA was demonstrated as the fold change relative to the control group 80 .…”

Biomarkers of chondrosarcoma

“…SIRT1 regulates the metastatic plasticity. 51 Chao et al have reported that SIRT1 signalling is induced by resveratrol, a natural phenolic compound found in several plants, 52 and induces human chondrosarcoma cell apoptosis. 53 Taken these reports, the role of SIRT1 in chondrosarcoma is still not clear.…”

Regulation of Apoptosis and Radiation Sensitization in Lung Cancer Cells via the Sirt1/NF-κB/Smac Pathway

“…Therefore, SirT1 plays many biological roles, including the inhibition of cell differentiation, cell cycle regulation, apoptosis inhibition and tumorigenesis [17,18]. Notably, the expression of SirT1 is upregulated in several cancers including leukemia, colon cancer, prostate cancer, and lung cancer [7,8,19,20]. However, the exact effect of SirT1 in cancer development is still unclear.…”

“…Sirtuin, the mammalian silent information regulator 1 family, is a molecular family that includes seven members (SirT1 to SirT7, respectively) and shares extensive homologies with the silent information regulator 2 (sir2) gene in yeast [7]. SirT1, located in the cell nucleus, is the closest homologue of sir2 and a well-documented member of the sirtuin family [8].…”

“…Many studies have shown that SirT1 plays a major role in the regulation of cell survival and stress responses, such as responses to oxidative stress, nutrient starvation or calorie restriction, and DNA damage [7,[9][10][11][12][13]. SirT1, as a NAD + -dependent histone deacetylase, has a remarkably wide spectrum of substrates that not only interacts with and regulates histone H1, H3 and H4, but also with non-histone substrates such as nuclear factor-κB family, tumor suppressor p53, Ku70, fork-head transcription factors (i.e., FOXOS), and DNA repair factor E2F1 proteins [7,10,[14][15][16]. Therefore, SirT1 plays many biological roles, including the inhibition of cell differentiation, cell cycle regulation, apoptosis inhibition and tumorigenesis [17,18].…”