Abstract
BackgroundThe Polycomb group (PcG) genes are a class of regulators responsible for maintaining homeotic gene expression throughout cell division. PcG expression is deregulated in some types of human cancer. Both Bmi-1 and Mel-18 are of the key PcG proteins. We investigate the expression and clinicopathological roles of Mel-18 and Bmi-1 mRNA in gastric cancer.MethodsThe expression of Mel-18 and Bmi-1 in a series of 71 gastric cancer tissues and paired normal mucosal tissues distant from the tumorous lesion was assayed by quantitative real time RT-PCR. The correlation between Mel-18 and Bmi-1 mRNA expression, and between Mel-18 or Bmi-1 mRNA level and clinicopathological characteristics were analyzed.ResultsExpression of Mel-18 and Bmi-1 genes was variably detected, but overexpression of Bmi-1 mRNA and decreased expression of Mel-18 mRNA were the most frequent alteration. In addition, the expression of Bmi-1 and Mel-18 mRNA inversely correlates in gastric tumors. Moreover, a significant positive correlation between Bmi-1 overexpression and tumor size, depth of invasion, or lymph node metastasis, and a significant negative correlation between Mel-18 low-expression with lymph node metastasis or the clinical stage were observed.ConclusionOur data suggest that Mel-18 and Bmi-1 may play crucial but opposite roles in gastric cancer. Decreased Mel-18 and increased Bmi-1 mRNA expression was associated with the carcinogenesis and progression of gastric cancer. It is possible to list Bmi-1 and Mel-18 as biomarkers for predicting the prognosis of gastric cancer.
Highlights
The Polycomb group (PcG) genes are a class of regulators responsible for maintaining homeotic gene expression throughout cell division
The Polycomb group (PcG) genes were first identified in Drosophila as a class of regulators responsible for maintaining homeotic gene expression throughout cell division [1], PcG genes are conserved from Drosophila to mammals, and the expression levels of mammalian PcG genes differ between different tissues and cell types [2], PcG genes act as epigenetic silencers during embryo morphogenesis with a central role in the nervous system, heart, and skeleton development [3,4,5,6,7].In addition, PcG members have been involved in the regulation of such adult processes as the cell cycle, X-inactivation, and hematopoiesis [8,9,10,11,12,13,14]
We found that gastric tumor tissues expressed significantly higher Bmi-1 and lower Mel-18, and the expression of Mel-18 negatively correlated with Bmi-1; there was a significant positive correlation between Bmi-1 expression with lymph node metastasis, or clinical stage, but there was no obvious correlation between Mel-18 expression and clinicopathological factors; downregulation of Bmi-1 by Mel-18 overexpression or knockdown of Bmi-1 expression was accompanied by decreased transformed phenotype and migration ability in gastric cancer cell lines in in vitro study [33]
Summary
The Polycomb group (PcG) genes are a class of regulators responsible for maintaining homeotic gene expression throughout cell division. PcG expression is deregulated in some types of human cancer Both Bmi-1 and Mel-18 are of the key PcG proteins. PcG expression is deregulated in some types of human cancer [15].several PcG genes may regulate the self-renewal of specific stem. Bmi-1 is one of the key PcG proteins It was initially identified as an oncogene that cooperated with c-Myc in the generation of mouse pre-B-cell lymphomas. It is considered the first functional mammalian PcG protooncogene to be recognized, and it has been implicated in axial patterning, hematopoiesis, cell cycle regulation, and senescence [18,19,20,21]. Bmi-1 plays an important role in self-renewal of hematopoietic stem cells, neural stem cells and mammary stem cells [35,36,37]
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