Gan Yu1, Heng Li1, Ji Wang2, Kiranmai Gumireddy3, Anping Li3, Weimin Yao1, Kun Tang1, Wei Xiao1, Junhui Hu1, Haibing Xiao1, Bin Lang4, Zhangqun Ye1, Qihong Huang3, Hua Xu5. 1. Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. 2. Department of Cell Death and Cancer Genetics, The Hormel Institute, University of Minnesota, Austin, Minnesota. 3. The Wistar Institute, Philadelphia, Pennsylvania. 4. School of Health Sciences, Macao Polytechnic Institute, Macao, People's Republic of China. 5. Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China. Electronic address: xuhuawhu@163.com.
Abstract
PURPOSE: We investigated the potential functions of miR-34a in CD44 transcriptional complexes in renal cell carcinoma. MATERIALS AND METHODS: We detected miR-34a expression by quantitative real-time polymerase chain reaction. Oligonucleotides were used to over express miR-34a. Cell proliferation and xenograft assays, colony formation and flow cytometry were done to examine effects on cancer cell proliferation in vitro and in vivo. Luciferase assay was performed to verify the precise target of miR-34a. RESULTS: Promoter methylation contributed to miR-34a loss in the ACHN, 786-O and SN12PM6 renal carcinoma cell lines. Ectopic over expression of miR-34a restrained cell growth, tube formation and migration/invasion, and significantly suppressed the growth of renal carcinoma xenografts and metastasis in nude mice. Dual luciferase assay revealed that CD44 was a direct target of miR-34a in renal cancer cells and CD44 knockdown by RNAi in renal cancer cells suppressed tumor progression. In contrast, CD44 ectopic expression partially reversed the antitumor effects of miR-34a in renal cancer cells. CONCLUSIONS: Our findings indicate that miR-34a targets CD44 in renal cancer cells and suppresses renal cancer cell growth, tube formation and metastasis in vitro and in vivo. Thus, miR-34a may be a potential molecular target for novel therapeutic strategies for clear cell renal carcinoma.
PURPOSE: We investigated the potential functions of miR-34a in CD44 transcriptional complexes in renal cell carcinoma. MATERIALS AND METHODS: We detected miR-34a expression by quantitative real-time polymerase chain reaction. Oligonucleotides were used to over express miR-34a. Cell proliferation and xenograft assays, colony formation and flow cytometry were done to examine effects on cancer cell proliferation in vitro and in vivo. Luciferase assay was performed to verify the precise target of miR-34a. RESULTS: Promoter methylation contributed to miR-34a loss in the ACHN, 786-O and SN12PM6 renal carcinoma cell lines. Ectopic over expression of miR-34a restrained cell growth, tube formation and migration/invasion, and significantly suppressed the growth of renal carcinoma xenografts and metastasis in nude mice. Dual luciferase assay revealed that CD44 was a direct target of miR-34a in renal cancer cells and CD44 knockdown by RNAi in renal cancer cells suppressed tumor progression. In contrast, CD44 ectopic expression partially reversed the antitumor effects of miR-34a in renal cancer cells. CONCLUSIONS: Our findings indicate that miR-34a targets CD44 in renal cancer cells and suppresses renal cancer cell growth, tube formation and metastasis in vitro and in vivo. Thus, miR-34a may be a potential molecular target for novel therapeutic strategies for clear cell renal carcinoma.
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