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Sgo1 is a potential therapeutic target for hepatocellular carcinoma.

Wang LH, Yen CJ, Li TN, Elowe S, Wang WC, Wang LH - Oncotarget (2015)

Bottom Line: Shugoshin-like protein 1 (Sgo1) is an essential protein in mitosis; it protects sister chromatid cohesion and thereby ensures the fidelity of chromosome separation.In contrast, cell viability and mitotic progression of immortalized cells were not significantly affected.Notably, mitotic cell death induced upon Sgo1 depletion was suppressed upon inhibitions of cyclin-dependent kinase-1 and Aurora kinase-B, or the depletion of mitotic arrest deficient-2.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan.

ABSTRACT
Shugoshin-like protein 1 (Sgo1) is an essential protein in mitosis; it protects sister chromatid cohesion and thereby ensures the fidelity of chromosome separation. We found that the expression of Sgo1 mRNA was relatively low in normal tissues, but was upregulated in 82% of hepatocellular carcinoma (HCC), and correlated with elevated alpha-fetoprotein and early disease onset of HCC. The depletion of Sgo1 reduced cell viability of hepatoma cell lines including HuH7, HepG2, Hep3B, and HepaRG. Using time-lapse microscopy, we showed that hepatoma cells were delayed and ultimately die in mitosis in the absence of Sgo1. In contrast, cell viability and mitotic progression of immortalized cells were not significantly affected. Notably, mitotic cell death induced upon Sgo1 depletion was suppressed upon inhibitions of cyclin-dependent kinase-1 and Aurora kinase-B, or the depletion of mitotic arrest deficient-2. Thus, mitotic cell death induced upon Sgo1 depletion in hepatoma cells is mediated by persistent activation of the spindle assembly checkpoint. Together, these results highlight the essential role of Sgo1 in the maintenance of a proper mitotic progression in hepatoma cells and suggest that Sgo1 is a promising oncotarget for HCC.

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Tissue and cell line expression profiles of Sgo1(A) Quantitative real-time PCR analysis of Sgo1 mRNA in HeLa cells and 16 normal tissues as indicated. The Y-axis represents the fold change in the expression of Sgo1 mRNA relative to that in HeLa cells and after normalization with levels of gapdh. (B) Protein expressions of Sgo1 and β-actin were examined in eight transformed cell lines (HeLa, HCT-116, 293T, WRL-68, and HuH-7, HepG2, Hep3B, ad HepaRG) and two immortalized cell lines (RPE-1 and NeHepLxHT). (C) Quantitation results of Sgo1 protein levels in these cell lines were shown. Asterisks represent a significance difference by Student's t-test (*, P < 0.05; **, P < 0.01).
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Figure 1: Tissue and cell line expression profiles of Sgo1(A) Quantitative real-time PCR analysis of Sgo1 mRNA in HeLa cells and 16 normal tissues as indicated. The Y-axis represents the fold change in the expression of Sgo1 mRNA relative to that in HeLa cells and after normalization with levels of gapdh. (B) Protein expressions of Sgo1 and β-actin were examined in eight transformed cell lines (HeLa, HCT-116, 293T, WRL-68, and HuH-7, HepG2, Hep3B, ad HepaRG) and two immortalized cell lines (RPE-1 and NeHepLxHT). (C) Quantitation results of Sgo1 protein levels in these cell lines were shown. Asterisks represent a significance difference by Student's t-test (*, P < 0.05; **, P < 0.01).

Mentions: To investigate the status of Sgo1 expression in various human tissues, we measured the mRNA level of Sgo1 by quantitative real-time-PCR using primers covering the full-length A1/A2 isoforms. Sgo1 mRNA was mostly expressed in thymus, testis, and spleen. The mRNA level of Sgo1 is low in the majority of normal tissues, including heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, colon, prostate, ovary, small intestine, and leukocytes (Fig. 1A). Next, to explore the potential role of Sgo1 in the development of human malignancies, we compared Sgo1 protein expression in eight transformed (HeLa, HCT-116, 293T, WRL-68, HuH-7, HepG2, Hep3B, and HepaRG) and two immortalized (RPE-1 and NeHepLxHT) cell lines expressing human telomerase reverse transcriptase. Sgo1 was detected in all cell lines with different expression levels (Fig. 1B). Notably, among the six hepatocyte-derived cell lines, hepatoma cell lines expressed 3-10-fold higher levels of Sgo1 when compared with immortalized NeHepLxHT cells (Fig. 1C). Similarly, RPE-1 cells displayed a relatively lower level of Sgo1 when compared other transformed cells. Together, all eight transformed cell lines displayed a relatively higher level of Sgo1 in comparison to two non-transformed cell lines.


Sgo1 is a potential therapeutic target for hepatocellular carcinoma.

Wang LH, Yen CJ, Li TN, Elowe S, Wang WC, Wang LH - Oncotarget (2015)

Tissue and cell line expression profiles of Sgo1(A) Quantitative real-time PCR analysis of Sgo1 mRNA in HeLa cells and 16 normal tissues as indicated. The Y-axis represents the fold change in the expression of Sgo1 mRNA relative to that in HeLa cells and after normalization with levels of gapdh. (B) Protein expressions of Sgo1 and β-actin were examined in eight transformed cell lines (HeLa, HCT-116, 293T, WRL-68, and HuH-7, HepG2, Hep3B, ad HepaRG) and two immortalized cell lines (RPE-1 and NeHepLxHT). (C) Quantitation results of Sgo1 protein levels in these cell lines were shown. Asterisks represent a significance difference by Student's t-test (*, P < 0.05; **, P < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385833&req=5

Figure 1: Tissue and cell line expression profiles of Sgo1(A) Quantitative real-time PCR analysis of Sgo1 mRNA in HeLa cells and 16 normal tissues as indicated. The Y-axis represents the fold change in the expression of Sgo1 mRNA relative to that in HeLa cells and after normalization with levels of gapdh. (B) Protein expressions of Sgo1 and β-actin were examined in eight transformed cell lines (HeLa, HCT-116, 293T, WRL-68, and HuH-7, HepG2, Hep3B, ad HepaRG) and two immortalized cell lines (RPE-1 and NeHepLxHT). (C) Quantitation results of Sgo1 protein levels in these cell lines were shown. Asterisks represent a significance difference by Student's t-test (*, P < 0.05; **, P < 0.01).
Mentions: To investigate the status of Sgo1 expression in various human tissues, we measured the mRNA level of Sgo1 by quantitative real-time-PCR using primers covering the full-length A1/A2 isoforms. Sgo1 mRNA was mostly expressed in thymus, testis, and spleen. The mRNA level of Sgo1 is low in the majority of normal tissues, including heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, colon, prostate, ovary, small intestine, and leukocytes (Fig. 1A). Next, to explore the potential role of Sgo1 in the development of human malignancies, we compared Sgo1 protein expression in eight transformed (HeLa, HCT-116, 293T, WRL-68, HuH-7, HepG2, Hep3B, and HepaRG) and two immortalized (RPE-1 and NeHepLxHT) cell lines expressing human telomerase reverse transcriptase. Sgo1 was detected in all cell lines with different expression levels (Fig. 1B). Notably, among the six hepatocyte-derived cell lines, hepatoma cell lines expressed 3-10-fold higher levels of Sgo1 when compared with immortalized NeHepLxHT cells (Fig. 1C). Similarly, RPE-1 cells displayed a relatively lower level of Sgo1 when compared other transformed cells. Together, all eight transformed cell lines displayed a relatively higher level of Sgo1 in comparison to two non-transformed cell lines.

Bottom Line: Shugoshin-like protein 1 (Sgo1) is an essential protein in mitosis; it protects sister chromatid cohesion and thereby ensures the fidelity of chromosome separation.In contrast, cell viability and mitotic progression of immortalized cells were not significantly affected.Notably, mitotic cell death induced upon Sgo1 depletion was suppressed upon inhibitions of cyclin-dependent kinase-1 and Aurora kinase-B, or the depletion of mitotic arrest deficient-2.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan.

ABSTRACT
Shugoshin-like protein 1 (Sgo1) is an essential protein in mitosis; it protects sister chromatid cohesion and thereby ensures the fidelity of chromosome separation. We found that the expression of Sgo1 mRNA was relatively low in normal tissues, but was upregulated in 82% of hepatocellular carcinoma (HCC), and correlated with elevated alpha-fetoprotein and early disease onset of HCC. The depletion of Sgo1 reduced cell viability of hepatoma cell lines including HuH7, HepG2, Hep3B, and HepaRG. Using time-lapse microscopy, we showed that hepatoma cells were delayed and ultimately die in mitosis in the absence of Sgo1. In contrast, cell viability and mitotic progression of immortalized cells were not significantly affected. Notably, mitotic cell death induced upon Sgo1 depletion was suppressed upon inhibitions of cyclin-dependent kinase-1 and Aurora kinase-B, or the depletion of mitotic arrest deficient-2. Thus, mitotic cell death induced upon Sgo1 depletion in hepatoma cells is mediated by persistent activation of the spindle assembly checkpoint. Together, these results highlight the essential role of Sgo1 in the maintenance of a proper mitotic progression in hepatoma cells and suggest that Sgo1 is a promising oncotarget for HCC.

Show MeSH
Related in: MedlinePlus