Deregulated expression of sprouty2 and microRNA-21 in human colon cancer Correlation with the clinical stage of the disease

被引:84
作者
Feng, Yin-Hsun [1 ,3 ,4 ,6 ]
Wu, Chao-Liang [1 ,2 ]
Tsao, Chao-Jung [5 ]
Chang, Jan-Gowth [7 ]
Lu, Pei-Jung [1 ]
Yeh, Kun-Tu [8 ]
Uen, Yih-Huei
Lee, Jeng-Chang [1 ]
Shiau, Ai-Li [1 ]
机构
[1] Natl Cheng Kung Univ, Coll Med, Inst Clin Med, Tainan 70101, Taiwan
[2] Natl Cheng Kung Univ, Coll Med, Dept Biochem & Mol Biol, Tainan 70101, Taiwan
[3] Chi Mei Med Ctr, Div Hematol & Oncol, Yong Kang City, Taiwan
[4] Chi Mei Med Ctr, Dept Internal Med, Yong Kang City, Taiwan
[5] Chi Mei Med Ctr, Div Hematol & Oncol, Liouying, Taiwan
[6] Chung Hwa Univ Med Technol, Coll Med & Life Sci, Tainan, Taiwan
[7] Kaohsiung Med Univ Hosp, Dept Lab Med, Kaohsiung, Taiwan
[8] Changhua Christian Hosp, Dept Surg Pathol, Changhua, Taiwan
关键词
sprouty2; microRNA-21; colon cancer; cancer stage; tumor suppressor; METASTATIC COLORECTAL-CANCER; CETUXIMAB PLUS IRINOTECAN; GROWTH-FACTOR RECEPTOR; TUMOR-SUPPRESSOR GENE; DOWN-REGULATION; CELL-PROLIFERATION; PROTEIN; KINASE; INHIBITOR; CARCINOMA;
D O I
10.4161/cbt.11.1.13965
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Sprouty protein is a novel feedback regulator involved in downstream inactivation of several growth factor receptor pathways. Sprouty2 (Spry2) protein was shown to be downregulated in human cancers. High levels of microRNA-21 (miRNA-21) expression have been associated with poor survival and poor response to adjuvant chemotherapy in cancer patients. But the effect of Spry2 in human colon cancer remained unknown. Paired tumor and normal mucosa samples from patients were examined for their expression of Spry2 mRNA and miRNA-21 by real-time quantitative RT-PCR analysis. Our results show that Spry2 was downregulated in human colon cancer, and its expression levels were lower in advanced-stage tumors than in early-stage tumors. There was a negative correlation between the expression levels of Spry2 and miRNA-21. Furthermore, overexpression of Spry2 suppressed the growth and migration of colon cancer cells with a concomitant increase in PTEN expression and reduction of Akt and MAPK phosphorylation. Spry2 inhibited the growth and tumorigenesis of colon cancer cells in vivo. Conclusively, we show for the first time that Spry2 expression is downregulated and miRNA-21 is upregulated in the clinical samples of colon cancer, which correlates with clinical stage of disease. Thus, Spry2 functions as a tumor suppressor in colon cancer.
引用
收藏
页码:111 / 121
页数:11
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