MiR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis.
MiR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis.
复制标题
MiR-1 下调与透明细胞肾细胞癌的低生存率相关，它会干扰细胞周期调节和转移。
DOI：
10.18632/oncotarget.3915
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发表时间：
2015-05-30
期刊：
影响因子：
--
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Xiao H;Zeng J;Li H;Chen K;Yu G;Hu J;Tang K;Zhou H;Huang Q;Li A;Li Y;Ye Z;Wang J;Xu H
与致癌作用密切相关的微小RNA（miRNA）最近重塑了我们对非编码RNA作用的理解。本文就miR-1的功能、分子机制及其在肾透明细胞癌（ccRCC）中的应用进行综述。首先，与相应的非癌组织（NCT）相比，87.8%的肾癌样本中miR-1显著下调，这与临床分期、T分类和总生存率显著相关。功能研究表明，miR-1在肾癌细胞中的强制过表达在体外和体内抑制增殖和转移。相反，miR-1抑制剂沉默miR-1表达促进ccRCC中的细胞增殖和转移。CDK 4、CDK 6、Caprin 1和Slug分别被miR-1直接靶向抑制，恢复它们的表达逆转了miR-1介导的细胞周期进展和转移的抑制。综上所述，我们的研究结果确立了miR-1通过靶向CDK 4、CDK 6、Caprin 1和Slug在ccRCC进展中的肿瘤抑制作用，并表明miR-1可以作为ccRCC的新的潜在治疗靶点。
MicroRNAs (miRNA) that are strongly implicated in carcinogenesis have recently reshaped our understanding of the role of noncoding RNAs. Here, we focused on the function and molecular mechanism of miR-1 and its potential clinical application in clear cell renal cell carcinoma (ccRCC). First, miR-1 was significantly downregulated in 87.8% renal cancer samples compared with corresponding noncancerous tissues (NCT), which was significantly associated with clinical stage, T classification and poor overall survival. Functional study demonstrated that enforced overexpression of miR-1 in renal cancer cells inhibited proliferation and metastasis in vitro and in vivo. Conversely, miR-1 inhibitor silencing miR-1 expression promoted cell proliferation and metastasis in ccRCC. CDK4, CDK6, Caprin1 and Slug were each directly targeted for inhibition by miR-1 and restoring their expression reversed miR-1-mediated inhibition of cell cycle progression and metastasis. Taken together, our findings established a tumor suppressive role for miR-1 in the progression of ccRCC by targeting CDK4, CDK6, Caprin1 and Slug and suggested miR-1 can be served as a novel potential therapeutic target for ccRCC.