Basic Research - Cancer(구연) (E-019)

진행성 투명세포 신세포암의 바이오 마커, DEAD/DEAH box helicase, DDX11
연세의대 신촌세브란스병원
박지수, 이명은, 장원식, 김종찬, 이승환, 나군호, 함원식
BACKGROUND: DDX11, the essential for sister chromatid cohesion, has been clinically identified as the key biomarker in predicting tumor aggressiveness in clinically localized T1-stage clear cell renal cell carcinoma (ccRCC) in our previous studies. However, no basic studies have been conducted to elucidate the role of DDX11 in RCC development and progression.

OBJECTIVES: In this study, we have demonstrated the role of DDX11 in RCC development and progression.

MATERIALS & METHODS: Immunohistochemistry and immunoblot analysis were performed, determining expressions of DDX11 in ccRCC patient tissues and cell lines. Following transfection of ccRCC cell lines with a DDX11-specific siRNA, qPCR and western blot analysis were conducted to determine downregulation of DDX11 in the transfected ccRCC cells. In subsequent studies, we have assessed the impact of suppressing DDX11 expression on ccRCC cell lines through proliferation analysis and apoptosis assays.

RESULTS: The findings of this study presented that DDX11 is upregulated with progression from low-grade to high-grade ccRCC, which was highly expressed in advanced ccRCCs. Furthermore, we have demonstrated that blocking the expression of DDX11 leads to inhibition of ccRCC cell proliferation and severe defects in chromosome segregation, eventually leading to rapid and massive apoptosis of ccRCC cells.

CONCLUSIONS: To our knowledge, not many studies have been conducted in the role of helicases in ccRCC development and progression of early to advanced status. In this study, we have reported the high levels of DDX11 expressions in high-grade and metastatic ccRCCs. Moreover, we have demonstrated the role of interfering DDX11 expression which leads to severe chromosome segregation defects and massive apoptosis. These findings suggest the role of DDX11 as the biomarker for molecular targeted therapy for advanced ccRCCs.
keywords : DDX11, renal cell carcinoma, clear cell

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