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http://dx.doi.org/10.14348/molcells.2014.0081

RNA Interference-Mediated Knockdown of Astrocyte Elevated Gene-1 Inhibits Growth, Induces Apoptosis, and Increases the Chemosensitivity to 5-Fluorouracil in Renal Cancer Caki-1 Cells  

Wang, Peng (The Second Department of Urology, Shengjing Hospital of China Medical University)
Yin, Bo (The Second Department of Urology, Shengjing Hospital of China Medical University)
Shan, Liping (The Second Department of Urology, Shengjing Hospital of China Medical University)
Zhang, Hui (The Second Department of Urology, Shengjing Hospital of China Medical University)
Cui, Jun (The Second Department of Urology, Shengjing Hospital of China Medical University)
Zhang, Mo (The Second Department of Urology, Shengjing Hospital of China Medical University)
Song, Yongsheng (The Second Department of Urology, Shengjing Hospital of China Medical University)
Publication Information
Molecules and Cells / v.37, no.12, 2014 , pp. 857-864 More about this Journal
Abstract
Astrocyte elevated gene-1 (AEG-1) is a recently discovered oncogene that has been reported to be highly expressed in various types of malignant tumors, including renal cell carcinoma. However, the precise role of AEG-1 in renal cancer cell proliferation and apoptosis has not been clarified. In this study, we transfected the renal cancer cell line Caki-1 with a plasmid expressing AEG-1 short hairpin RNA (shRNA) and obtained cell colonies with stable knockdown of AEG-1. We found that AEG-1 down-regulation inhibited cell proliferation and colony formation and arrested cell cycle progression at the sub-G1 and G0/G1 phase. Western blot analysis indicated that the expression of proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E were significantly reduced following AEG-1 down-regulation. In addition, AEG-1 knockdown led to the appearance of apoptotic bodies in renal cancer cells, and the ratio of apoptotic cells significantly increased. Expression of the antiapoptotic factor Bcl-2 was dramatically reduced, whereas the pro-apoptotic factors Bax, caspase-3 and poly (ADPribose) polymerase (PARP) were significantly activated. Finally, AEG-1 knockdown in Caki-1 cells remarkably suppressed cell proliferation and enhanced cell apoptosis in response to 5-fluorouracil (5-FU) treatment, suggesting that AEG-1 inhibition sensitizes Caki-1 cells to 5-FU. Taken together, our data suggest that AEG-1 plays an important role in renal cancer formation and development and may be a potential target for future gene therapy for renal cell carcinoma.
Keywords
apoptosis; astrocyte elevated gene-1; chemosensitivity; proliferation; renal cancer cells;
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