Transcriptional Regulation and Biological Functions of Selenium-Binding Protein 1 in Colorectal Cancer In Vitro and in Nude Mouse Xenografts

Abstract

BackgroundIt has been shown that selenium-binding protein 1 (SBP1) is significantly downregulated in different human cancers. Its regulation and function have not yet been established.Methodology and Principal FindingsWe show that the SBP1 promoter is hypermethylated in colon cancer tissues and human colon cancer cells. Treatment with 5′-Aza-2′-deoxycytidine leads to demethylation of the SBP1 promoter and to an increase of SBP1 promoter activity, rescues SBP1 mRNA and protein expression in human colon cancer cells. Additionally, overexpression of SBP1 sensitizes colon cancer cells to H2O2-induced apoptosis, inhibits cancer cell migration in vitro and inhibits tumor growth in nude mice.Conclusion and SignificanceThese data demonstrate that SBP1 has tumor suppressor functions that are inhibited in colorectal cancer through epigenetic silencing.

Reduced selenium-binding protein 1 is associated with poor survival rate in gastric carcinoma

“…Although we have not demonstrated clearly the mechanisms underlined the tumor suppressor functions of SBP1, it has been evidenced that SBP1 promoter was hypermethylated in human colon cancer cells and indicated that SBP1 expression in colon cancer was in part controlled through gene silencing [23]. Although decreased expression of SBP1 was demonstrated in GC, more evidence should be provided to identify the tumor suppressive activities of SBP1.…”

“…SBP1 expression was also closely correlated to the prognosis of many malignant tumors. And recently, overexpression of SBP1 in human colon cancer cell line HCT116 was identified to induce H2O2-mediated apoptosis, inhibit cell migration in vitro and inhibit tumor growth in nude mice, which provide the evidence to show that SBP1 has anti-cancer functions [23]. Furthermore, SBP1 was characterized as a biomarker for schizophrenia [24].…”

Reduction of selenium-binding protein 1 sensitizes cancer cells to selenite via elevating extracellular glutathione: A novel mechanism of cancer-specific cytotoxicity of selenite

“…Reduced expression of SBP1 is also associated with poor clinical prognosis among patients with lung adenocarcinoma [30], gastric cancer [36], hepatocellular carcinoma [27], colon cancer [37,38], and breast cancer [41]. Furthermore, our in vitro and in vivo studies have also shown that increasing SBP1 expression in colorectal cancer cells attenuates cancer cell migration and tumor growth in nude mice [42]. Consistent with these findings, knockdown of SBP1 by small interfering RNA (siRNA) in the nontransformed human liver cells results in a substantial increase in cell proliferation index and migration capacity [27], suggesting that SBP1 acts as a tumor suppressor [43], which is further supported by the recent study that SBP1 negatively regulates HIF-1α expression and suppresses the malignant phenotype of prostate cancer cells [44].…”

Hepatic proteome changes in Solea senegalensis exposed to contaminated estuarine sediments: a laboratory and in situ survey

“…It is therefore not clear why this protein appeared downregulated after exposure to sediment C 1 , in the laboratory, comparatively to reference (R-tested) animals. Interestingly, downregulation of SBP1 has been found linked to carcinogenesis in mammal models and it is suspected that this protein mediated ROS (reactive oxygen species) -induced apoptosis of neoplasic or preneoplasic cells (for instance Pohl et al 2009). In accordance, some evidence exists on SBP1 downregulation by oxidative stress (Giometti et al 2000).…”