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MicroRNA-205 suppresses the oral carcinoma oncogenic activity via down-regulation of Axin-2 in KB human oral cancer cell
Authors:Jae-Sung Kim  Sun-Young Park  Seul Ah Lee  Min-Gyeong Park  Sun-Kyoung Yu  Myoung-Hwa Lee  Mi-Ra Park  Su-Gwan Kim  Ji-Su Oh  Sook-Young Lee  Chun Sung Kim  Heung-Joong Kim  Hong Sung Chun  Jin-Soo Kim  Sung-Min Moon  Do Kyung Kim
Affiliation:1. Oral Biology Research Institute, School of Dentistry, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju, 501-759, Republic of Korea
2. Department of Biotechnology, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju, 501-759, Republic of Korea
Abstract:MicroRNA (miRNA) is a small noncoding RNA molecule, 19–25 nucleotides in length, which regulates several pathways including cell development, cell proliferation, carcinogenesis, apoptosis, etc. In this study, the over-expression of microRNA-205 (miR-205) increased the number of apoptotic cells by at least 4 times compared to the control. In addition, over-expressed miRNA in KB oral cancer cells triggered apoptosis via the caspase cascade, including the cleavage of caspase-9, caspase-7, caspase-3, and PARP. Flow cytometry showed that apoptotic cell death was increased significantly by 35.33 % in KB oral cancer cells with over-expressed miR-205 compared to the control. The microarray data showed that axis inhibitor protein 2 (Axin2) was down-regulated in KB oral cancer cells transfected with miR-205. In addition, Axin2 was down-regulated by approximately 50 % by over-expressed miR-205 at both the mRNA and protein levels. Interestingly, Axin2 was up-regulated in KB oral cancer compared to human normal oral keratinocytes. Furthermore, the cell cytotoxicity and apoptotic population of KB oral cancer cells were increased significantly after Axin2 siRNA transfection. These results suggest that Axin2 is might be as potential oncogene in KB oral cancer cells. The luciferase assay showed that over-expressed miR-205 in KB oral cancer cells suppressed AXIN2 expression through an interaction with its own binding site at AXIN2 3′UTR (64–92). These results suggest that miR-205 is a novel anti-oncogenic miRNA in KB oral cancer cells, and may have potential applications in oral cancer therapy.
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