IRF6在腎臟細胞癌中的變異與探討
陳映慈1、馮思中2、張英勛2、謝瑾瑄2、莊正鏗2、翁文慧1*
1國立台北科技大學 化學工程與生物科技系;2林口長庚醫院 外科部 泌尿科
ABERRANT EXPRESSION OF IRF6 IN RENAL CELL CARCINOMA
Ying-Tzu Chen1, See-Tong Pang2, Ying-Hsu Chang2, Chin-Hsuan Hsieh2,
Cheng-Keng Chuang2, Wen-Hui Weng1*
1Department of Chemical Engineering and Biotechnology and Graduate Institute of Biochemical and Biomedical Engineering, National Taipei University of Technology, Taipei, Taiwan.
2Division of Urology, Department of Surgery, Chang Gung Memorial Hospital,
Chang Gung University, Taiwan.
*Corresponding author
Purpose: According to our previous results in methylated-CpG island recovery assay (MIRA) and RNA expression array, methylated status of Interferon regulatory factor 6 (IRF6) could be observed in most of renal cell carcinoma (RCC) cases, and presented a negative correlation with gene expression, especially in clear cell type of RCCs. The aim of this study is to clarify the clinical significance and role of IRF6 in RCC.
Materials and Methods: 105 pairs of clinical RCC patients and RCC cell lines have involved in the current study. Real-time PCR assay was used to detect the expression of IRF6 on all cases. Western blot assay was performed to detect whether the expression of IRF6 in the 5-aza-2’deoxycytidine treated RCC cells could be restored. The IRF6 gene expression level in normal and RCC tissues were shown by –ΔCT and applied by the paired- T test.
Results: The variant and lower level gene expression of the IRF6 could be observed in most of RCC cell lines. After cells treated with 5-aza-2’deoxycytidine, the expression of IRF6 was restored. In the real-time PCR of IRF6 in RCC tissues, the mean –ΔCT was -8.0 in normal tissue and -11.5 in RCC tissue with significantly different (P=0.013).
Conclusions: Our findings demonstrated that the aberrant expression of IRF6 in RCCs was due to methylation. Also, the expression level of IRF6 was higher in normal tissues as compared with tumor tissues. Besides, it has been described that IRF6 could function as a tumor suppressor since it could inhibit tumor invasion and migration in squamous cell carcinoma. Based on these results, we suggest that IRF6 may play an important role in the pathophysiology of RCC. However, further cell viability and correlation with the clinical information should be further analyzed in the future.