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MicroRNA-590-5p 通过靶向 PBRM1 增强肾透明细胞癌细胞的增殖和侵袭。

Enhancement of proliferation and invasion by MicroRNA-590-5p via targeting PBRM1 in clear cell renal carcinoma cells.

机构信息

Xiangya Hospital, Central-South University, Changsha, China.

出版信息

Oncol Res. 2013;20(11):537-44. doi: 10.3727/096504013X13775486749335.

DOI:10.3727/096504013X13775486749335
PMID:24063284
Abstract

MicroRNAs (miRNAs) play an important role in cancer development. In our study, miR-590-5p is found to be upregulated in the examined renal cell carcinoma (RCC) cell lines. PBRM1 acts as tumor suppressor in RCC, and its downregulation is associated with increased proliferation and aggressive behavior in RCC. We confirmed that PBRM1 was a direct target of miR-590-5p. miR-590-5p could regulate PBRM1 mRNA and protein expressions in clear cell renal carcinoma (ccRCC) ACHN and 786-O cells. Downregulation of miR-590-5p, which resulted in increased PBRM1, inhibited proliferation and invasion of ccRCC cells. Upregulation of miR-590-5p, which resulted in decreased PBRM1, promoted proliferation and invasion of ccRCC cells. The process of miR-590-5p promoting proliferation was found to be implicated in its inhibition of G1/S transition of ccRCC cells, and the action mechanisms were involved in its downregulation of PBRM1/p21(WAF1/CIP1) expression. In conclusion, we identified the role of miR-590-5p, serving as an oncomir in ccRCC, and our findings provide a potential target for the treatment of ccRCC.

摘要

微小 RNA(miRNAs)在癌症发展中发挥着重要作用。在我们的研究中,发现 miR-590-5p 在被检测的肾细胞癌(RCC)细胞系中上调。PBRM1 在 RCC 中作为肿瘤抑制因子,其下调与 RCC 中增殖和侵袭行为的增加有关。我们证实 PBRM1 是 miR-590-5p 的直接靶标。miR-590-5p 可以调节 clear cell renal carcinoma(ccRCC)ACHN 和 786-O 细胞中的 PBRM1 mRNA 和蛋白表达。下调 miR-590-5p 导致 PBRM1 增加,抑制 ccRCC 细胞的增殖和侵袭。上调 miR-590-5p 导致 PBRM1 减少,促进 ccRCC 细胞的增殖和侵袭。miR-590-5p 促进增殖的过程被发现与其抑制 ccRCC 细胞 G1/S 转换有关,其作用机制涉及下调 PBRM1/p21(WAF1/CIP1)表达。总之,我们确定了 miR-590-5p 在 ccRCC 中作为致癌 miRNA 的作用,我们的发现为 ccRCC 的治疗提供了一个潜在的靶点。

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