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微小RNA-155通过靶向E2F2调控肾透明细胞癌细胞的增殖和侵袭。

miR-155 regulates the proliferation and invasion of clear cell renal cell carcinoma cells by targeting E2F2.

作者信息

Gao Yu, Ma Xin, Yao Yuanxin, Li Hongzhao, Fan Yang, Zhang Yu, Zhao Chaofei, Wang Lei, Ma Minghui, Lei Zhengwei, Zhang Xu

机构信息

Department of Urology, Chinese PLA General Hospital/Chinese PLA Medical School, Beijing, 100853, P. R. China.

State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital/Chinese PLA Medical School, Beijing, 100853, P. R. China.

出版信息

Oncotarget. 2016 Apr 12;7(15):20324-37. doi: 10.18632/oncotarget.7951.

DOI:10.18632/oncotarget.7951
PMID:26967247
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4991458/
Abstract

MicroRNAs (miRNAs) have emerged as critical modulators of carcinogenesis and tumor progression. In the present work, we sought to identify the biological function of miR-155 as well as its underlying mechanism in clear cell renal cell carcinoma (ccRCC). We examined the expression of miR-155 in clear cell RCC (ccRCC) and adjacent normal tissues and then explored the roles of miR-155 both in vitro and in vivo. The results of this analysis indicated that miR-155 activity was significantly upregulated in ccRCC tissues compared with the corresponding normal tissues. miR-155 was associated with ccRCC aggressiveness in both cell lines and clinical specimens, and a specific and inverse correlation between miR-155 and E2F2 expression was found in human ccRCC samples. Overexpression of miR-155 in 786-O cells decreased E2F2 expression while reduction of miR-155 by anti-miR-155 in ACHN cells elevated E2F2 expression. Re-expression of E2F2 in 786-O cells repressed the cell migration/invasion abilities elevated by miR-155, whereas knockdown of E2F2 in ACHN cells restored these cellular functions hampered by the miR-155 inhibitor. Using Western blot and luciferase reporter assays, we determined that E2F2 was a direct target of miR-155. Taken together, the in vitro and in vivo results demonstrate that miR-155 functions as a tumor-promoting miRNA by targeting E2F2 in ccRCC.

摘要

微小RNA(miRNA)已成为癌症发生和肿瘤进展的关键调节因子。在本研究中,我们试图确定miR-155在透明细胞肾细胞癌(ccRCC)中的生物学功能及其潜在机制。我们检测了miR-155在透明细胞肾细胞癌(ccRCC)组织和相邻正常组织中的表达,然后在体外和体内探索了miR-155的作用。该分析结果表明,与相应的正常组织相比,ccRCC组织中miR-155的活性显著上调。miR-155在细胞系和临床标本中均与ccRCC的侵袭性相关,并且在人类ccRCC样本中发现miR-155与E2F2表达之间存在特定的负相关。在786-O细胞中过表达miR-155会降低E2F2的表达,而在ACHN细胞中用抗miR-155降低miR-155会提高E2F2的表达。在786-O细胞中重新表达E2F2可抑制miR-155升高的细胞迁移/侵袭能力,而在ACHN细胞中敲低E2F2可恢复被miR-155抑制剂阻碍的这些细胞功能。通过蛋白质免疫印迹和荧光素酶报告基因检测,我们确定E2F2是miR-155的直接靶标。综上所述,体外和体内结果表明,在ccRCC中,miR-155通过靶向E2F2发挥促肿瘤miRNA的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc61/4991458/179fcd8219ac/oncotarget-07-20324-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc61/4991458/6b285b38b7f6/oncotarget-07-20324-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc61/4991458/dc9f3a07557e/oncotarget-07-20324-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc61/4991458/7bf241d0a586/oncotarget-07-20324-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc61/4991458/efd33d02393e/oncotarget-07-20324-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc61/4991458/8254572b4a34/oncotarget-07-20324-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc61/4991458/179fcd8219ac/oncotarget-07-20324-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc61/4991458/6b285b38b7f6/oncotarget-07-20324-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc61/4991458/dc9f3a07557e/oncotarget-07-20324-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc61/4991458/7bf241d0a586/oncotarget-07-20324-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc61/4991458/efd33d02393e/oncotarget-07-20324-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc61/4991458/8254572b4a34/oncotarget-07-20324-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc61/4991458/179fcd8219ac/oncotarget-07-20324-g006.jpg

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