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Down-regulated expression of OPCML predicts an unfavorable prognosis and promotes disease progression in human gastric cancer

View Article: PubMed Central - PubMed

ABSTRACT

Background: OPCML belongs to the IgLON family of Ig domain–containing GPI-anchored cell adhesion molecules and was recently found to be involved in carcinogenesis, while its role in gastric cancer remains unclear.

Methods: We assessed expression and biological behavior of OPCML in gastric cancer.

Results: OPCML expression was markedly reduced in tumor tissues and cancer cell lines. Decreased OPCML expression had a significant association with unfavorable tumor stage (p = 0.007) and grading (p < 0.001). Furthermore, the results revealed that OPCML was an independent prognostic factor for overall survival in gastric cancer (p = 0.002). In addition, ectopic expression of OPCML in cancer cells significantly inhibited cell viability (p < 0.01) and colony formation (p < 0.001), arrest cell cycle in G0/G1 phase and induced apoptosis, and suppressed tumor formation in nude mice. The alterations of phosphorylation status of AKT and its substrate GSK3β, up-regulation of pro-apoptotic regulators including caspase-3, caspase-9 and PARP, and up-regulation of cell cycle regulator p27, were implicated in the biological activity of OPCML in cancer cells.

Conclusion: Down-regulated OPCML expression might serve as an independent predictor for unfavorable prognosis of patients, and the biological behavior supports its role as a tumor suppressor in gastric cancer.

Electronic supplementary material: The online version of this article (doi:10.1186/s12885-017-3203-y) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus

OPCML arrested cell cycle and induced apoptosis of gastric cancer cells. a1 and b1 Representative images of cell cycle distribution of SGC-7901 (a1) and BGC-823 (b1) cells. a2 and b2 Statistical analysis of the distribution percentage of cells in G0/G1, S, G2/M phases of SGC-7901 (a2) and BGC-823 (B2) cells. c1 and d1 Representative images of apoptosis of SGC-7901 (c1) and BGC-823 (d1) cells. c2 and d2 Statistical analysis of early apoptosis and late apoptosis ratio of SGC-7901 (c2) and BGC-823 (d2) cells. (Data are mean ± SE, versus empty vector; n = 5 independent experiments in triplicate). e changes of protein expression of G1/S phase transition regulator and the active form of pro-apoptosis regulators, as well as the phosphorylation levels of AKT and GSK3β in SGC-7901 and BGC-823 cells. ** P < 0.01,* P < 0.05
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Fig4: OPCML arrested cell cycle and induced apoptosis of gastric cancer cells. a1 and b1 Representative images of cell cycle distribution of SGC-7901 (a1) and BGC-823 (b1) cells. a2 and b2 Statistical analysis of the distribution percentage of cells in G0/G1, S, G2/M phases of SGC-7901 (a2) and BGC-823 (B2) cells. c1 and d1 Representative images of apoptosis of SGC-7901 (c1) and BGC-823 (d1) cells. c2 and d2 Statistical analysis of early apoptosis and late apoptosis ratio of SGC-7901 (c2) and BGC-823 (d2) cells. (Data are mean ± SE, versus empty vector; n = 5 independent experiments in triplicate). e changes of protein expression of G1/S phase transition regulator and the active form of pro-apoptosis regulators, as well as the phosphorylation levels of AKT and GSK3β in SGC-7901 and BGC-823 cells. ** P < 0.01,* P < 0.05

Mentions: The following cell cycle analysis by flow cytometry indicated that, after trasnfected with OPCML-pcDNA3.1 plasmid, an elevated percentage of both SGC-7901(from 35.5% to 60.5%, P < 0.01) and BGC-823 (from 45.3% to 68.8%, P < 0.01) cells accumulated in the G0/G1 phase, as compared to cells transfected with empty vector (Fig. 4a, b). While ectopic expression of OPCML led to a decreased proportion of cell population of both SGC-7901 and BGC-823 cells at S and G2/M phase (all P < 0.05) (Fig. 4a, b). These results revealed that OPCML suppressed proliferation of gastric cancer cells by arresting cell cycle in the G0/G1 phase.Fig. 4


Down-regulated expression of OPCML predicts an unfavorable prognosis and promotes disease progression in human gastric cancer
OPCML arrested cell cycle and induced apoptosis of gastric cancer cells. a1 and b1 Representative images of cell cycle distribution of SGC-7901 (a1) and BGC-823 (b1) cells. a2 and b2 Statistical analysis of the distribution percentage of cells in G0/G1, S, G2/M phases of SGC-7901 (a2) and BGC-823 (B2) cells. c1 and d1 Representative images of apoptosis of SGC-7901 (c1) and BGC-823 (d1) cells. c2 and d2 Statistical analysis of early apoptosis and late apoptosis ratio of SGC-7901 (c2) and BGC-823 (d2) cells. (Data are mean ± SE, versus empty vector; n = 5 independent experiments in triplicate). e changes of protein expression of G1/S phase transition regulator and the active form of pro-apoptosis regulators, as well as the phosphorylation levels of AKT and GSK3β in SGC-7901 and BGC-823 cells. ** P < 0.01,* P < 0.05
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Fig4: OPCML arrested cell cycle and induced apoptosis of gastric cancer cells. a1 and b1 Representative images of cell cycle distribution of SGC-7901 (a1) and BGC-823 (b1) cells. a2 and b2 Statistical analysis of the distribution percentage of cells in G0/G1, S, G2/M phases of SGC-7901 (a2) and BGC-823 (B2) cells. c1 and d1 Representative images of apoptosis of SGC-7901 (c1) and BGC-823 (d1) cells. c2 and d2 Statistical analysis of early apoptosis and late apoptosis ratio of SGC-7901 (c2) and BGC-823 (d2) cells. (Data are mean ± SE, versus empty vector; n = 5 independent experiments in triplicate). e changes of protein expression of G1/S phase transition regulator and the active form of pro-apoptosis regulators, as well as the phosphorylation levels of AKT and GSK3β in SGC-7901 and BGC-823 cells. ** P < 0.01,* P < 0.05
Mentions: The following cell cycle analysis by flow cytometry indicated that, after trasnfected with OPCML-pcDNA3.1 plasmid, an elevated percentage of both SGC-7901(from 35.5% to 60.5%, P < 0.01) and BGC-823 (from 45.3% to 68.8%, P < 0.01) cells accumulated in the G0/G1 phase, as compared to cells transfected with empty vector (Fig. 4a, b). While ectopic expression of OPCML led to a decreased proportion of cell population of both SGC-7901 and BGC-823 cells at S and G2/M phase (all P < 0.05) (Fig. 4a, b). These results revealed that OPCML suppressed proliferation of gastric cancer cells by arresting cell cycle in the G0/G1 phase.Fig. 4

View Article: PubMed Central - PubMed

ABSTRACT

Background: OPCML belongs to the IgLON family of Ig domain&ndash;containing GPI-anchored cell adhesion molecules and was recently found to be involved in carcinogenesis, while its role in gastric cancer remains unclear.

Methods: We assessed expression and biological behavior of OPCML in gastric cancer.

Results: OPCML expression was markedly reduced in tumor tissues and cancer cell lines. Decreased OPCML expression had a significant association with unfavorable tumor stage (p&nbsp;=&nbsp;0.007) and grading (p&nbsp;&lt;&nbsp;0.001). Furthermore, the results revealed that OPCML was an independent prognostic factor for overall survival in gastric cancer (p&nbsp;=&nbsp;0.002). In addition, ectopic expression of OPCML in cancer cells significantly inhibited cell viability (p&nbsp;&lt;&nbsp;0.01) and colony formation (p&nbsp;&lt;&nbsp;0.001), arrest cell cycle in G0/G1 phase and induced apoptosis, and suppressed tumor formation in nude mice. The alterations of phosphorylation status of AKT and its substrate GSK3&beta;, up-regulation of pro-apoptotic regulators including caspase-3, caspase-9 and PARP, and up-regulation of cell cycle regulator p27, were implicated in the biological activity of OPCML in cancer cells.

Conclusion: Down-regulated OPCML expression might serve as an independent predictor for unfavorable prognosis of patients, and the biological behavior supports its role as a tumor suppressor in gastric cancer.

Electronic supplementary material: The online version of this article (doi:10.1186/s12885-017-3203-y) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus