miRNA-34a suppresses cell proliferation and metastasis by targeting CD44 in human renal carcinoma cells.

miRNA-34a suppresses cell proliferation and metastasis by targeting CD44 in human renal carcinoma cells.
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miRNA-34a 通过靶向人肾癌细胞中的 CD44 抑制细胞增殖和转移

DOI:
10.1016/j.juro.2014.05.094
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发表时间:
2014-10
期刊:
J Urol
影响因子:
--
通讯作者:
Xu, Hua
Xu, Hua
中科院分区:
其他
文献类型:
--
作者:
Lang, Bin;Ye, Zhangqun;Huang, Qihong;Xu, Hua

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目的探讨miR-34 a在肾癌组织中的表达及其在CD 44转录复合物中的作用。使用寡核苷酸过表达miR-34 a。进行细胞增殖和异种移植测定、集落形成和流式细胞术以检查对体外和体内癌细胞增殖的影响。结果ACHN、786-O和SN 12 PM 6细胞株中miR-34 a基因启动子甲基化均导致miR-34 a的丢失。miR-34 a的过度表达抑制了细胞的生长、小管形成和迁移/侵袭,并显著抑制了肾癌裸鼠移植瘤的生长和转移。双荧光素酶检测显示,CD 44是miR-34 a在肾癌细胞中的直接靶点,RNAi敲低肾癌细胞中的CD 44可抑制肿瘤进展。相反,CD 44异位表达部分逆转了miR-34 a在肾癌细胞中的抗肿瘤作用。ConclusionsOur findings indicate,miR-34 a靶向于肾癌细胞中的CD 44,并抑制肾癌细胞的生长、小管形成和转移。因此,miR-34 a可能是肾透明细胞癌新的治疗策略的潜在分子靶点。
PurposeWe investigated the potential functions of miR-34a in CD44 transcriptional complexes in renal cell carcinoma.Materials and MethodsWe 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.ResultsPromoter 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.ConclusionsOur 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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