Gene expression profile analyze the molecular mechanism of CXCR7 regulating papillary thyroid carcinoma growth and metastasis

Journal of Experimental & Clinical Cancer Research

Zhen Liu¹  Lei Zhang¹  Zhangyi Liu¹  Xuyong Teng¹  Hengwei Zhang¹ 

[1] Department General Surgery, Affiliated Shenjing Hospital, China Medical University, No.36 Sanhao Street, Shenyang 110004, China

关键词: Signal pathway;    Gene microarray;    Metastasis;    Invasion;    CXCR7;    Chemokine receptor;    Thyroid carcinoma;   

Others  :  1133384
DOI  :  10.1186/s13046-015-0132-y

 received in 2014-10-12, accepted in 2015-02-02,  发布年份 2015

【 摘 要 】

Background

To detect genetic expression profile alterations after papillary thyroid carcinoma (PTC) cells transfected with chemokine receptor CXCR7 gene by gene microarray, and gain insights into molecular mechanisms of how CXCR7 regulating PTC growth and metastasis.

Methods

The Human OneArray microarray was used for a complete genome-wide transcript profiling of CXCR7 transfected PTCs (K1-CXCR7 cells), defined as experimental group. Non CXCR7 transfected PTCs (K1 cells) were used as control group. Differential analysis for per gene was performed with a random variance model and t test, p values were adjusted to control the false discovery rate. Gene ontology (GO) on differentially expressed genes to identify the biological processes in modulating the progression of papillary thyroid carcinoma. Pathway analysis was used to evaluate the signaling pathway that differentially expressed genes were involved in. In addition, quantitative real-time polymerase chain reaction (q-PCR) and Western blot were used to verify the top differentially expression genes.

Results

Comparative analysis revealed that the expression level of 1149 genes was changed in response to CXCR7 transfection. After unsupervised hierarchical clustering analysis, 270 differentially expressed genes were filtered, of them 156 genes were up-regulated whereas 114 genes were down-regulated in K1-CXCR7 cells. GO enrichment analysis revealed the differentially expressed genes were mainly involved in biopolymer metabolic process, signal transduction and protein metabolism. Pathway enrichment analysis revealed differentially expressed genes were mainly involved in ECM-receptor interaction, Focal adhesion, MAPK signaling pathway and Cytokine-cytokine receptor interaction pathway. More importantly, the expression level of genes closely associated with tumor growth and metastasis was altered significantly in K1-CXCR7 cells, including up-regulated genes FN1, COL1A1, COL4A1, PDGFRB, LTB, CXCL12, MMP-11, MT1-MMP and down-regulated genes ITGA7, and Notch-1.

Conclusions

Gene expression profiling analysis of papillary thyroid carcinoma can further delineate the mechanistic insights on how CXCR7 regulating papillary thyroid carcinoma growth and metastasis. CXCR7 may regulate growth and metastasis of papillary thyroid carcinoma via the activation of PI3K/AKT pathway and its downstream NF-κB signaling, as well as the down-regulation of Notch signaling.

【 授权许可】

   
2015 Zhang et al.; licensee BioMed Central.

【 图 表 】

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