HOXA11 gene is hypermethylation and aberrant expression in gastric cancer

Cancer Cell International

Shaoping Ji²  Zhimin Suo¹  Hui Zhang¹  Desheng Yang¹  Jiang Wu³  Yuhua Kang¹  Tingxun Gu²  Na Fang²  Yinguo Bai² 

[1] Department of Gastroenterology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China;Department of Biochemistry and Molecular Biology, Medical School of Henan University, Kaifeng 475004, Henan Province, China;Department of pathology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China

关键词: Expression;    Methylation;    HOXA11 gene;    Gastric cancer;   

Others  :  1121670
DOI  :  10.1186/s12935-014-0079-7

 received in 2014-03-18, accepted in 2014-07-29,  发布年份 2014

【 摘 要 】

Background

Aberrant DNA methylation is an acquired epigenetic alteration that serves as an alternative to genetic defects in the inactivation of tumor suppressor genes and other genes in diverse human cancers. Gastric carcinoma is one of the tumors with a high frequency of aberrant methylation in promoter region. Hence we investigated the promoter methylation status and expression level of HOXA11 gene which may involve in GC development.

Methods

Thirty-two surgical excised gastric cancer specimens, twelve paired adjacent non-cancerous specimens and seven normal gastric mucosas were examined. The methylation status and expression level of HOXA11 gene were determined by bisulfite sequencing polymerase chain reaction (BSP), real-time polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) respectively. HOXA11 expression was knocked-down with siRNA to mimic HOXA11 gene hypermethylation and ability of cell proliferation and migration was determinate. In addition, we analyzed and correlated the findings with clinicopathological features.

Results

The methylation level of HOXA11 gene in gastric cancer tissues and adjacent non-cancerous tissues were higher than those in normal gastric mucosa (P < 0.05). The methylation level was higher in TNM III and IV patients of GC than those in TNM I and II patients (P < 0.05). The expression of HOXA11 mRNA and protein decreased in normal gastric mucosa, peri-cancer tissue and GC (P < 0.05). HOXA11 expression was inversely correlated with DNA methylation (P < 0.05). Knocked-down of HOXA11 expression with siRNA in BGC-823 cells enhanced cell proliferation compared with control, but no significant different was observed in migration ability.

Conclusion

Hypermethylation and decreased expression of HOXA11 gene may be involved in the carcinogenesis and development of GC and may provide useful information for the prediction of the malignant behaviors of GC. And the expression of HOXA11 is impaired by DNA methylation. However, repression of HOXA11 expression promoted BGC-823 cell proliferation.

【 授权许可】

   
2014 Bai et al.; licensee Springer

【 图 表 】

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