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微小RNA-22通过Sp1负反馈环抑制结肠癌细胞的生长、迁移和侵袭。

MicroRNA-22 suppresses the growth, migration and invasion of colorectal cancer cells through a Sp1 negative feedback loop.

作者信息

Xia Shu-Sen, Zhang Guang-Jun, Liu Zuo-Liang, Tian Hong-Peng, He Yi, Meng Chang-Yuan, Li Li-Fa, Wang Zi-Wei, Zhou Tong

机构信息

The Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.

The Department of Gastrointestinal Surgery, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People's Republic of China.

出版信息

Oncotarget. 2017 May 30;8(22):36266-36278. doi: 10.18632/oncotarget.16742.

DOI:10.18632/oncotarget.16742
PMID:28422727
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5482653/
Abstract

MicroRNAs have recently emerged as regulators of many biological processes including cell proliferation, development and differentiation. This study identified that miR-22 was statistically decreased in colorectal cancer clinical specimens and highly metastatic cell lines. Moreover, low miR-22 expression was associated with tumor metastasis, advanced clinical stage and relapse. Consistent with clinical observations, miR-22 significantly suppressed the ability of colorectal cancer cells to growth and metastasize in vitro and in vivo. Sp1 was validated as a target of miR-22, and ectopic expression of Sp1 compromised the inhibitory effects of miR-22. In addition, Sp1 repressed miR-22 transcription by binding to the miR-22 promoter, hence forming a negative feedback loop. Further study has shown that miR-22 suppresses the activity of PTEN/AKT pathway by Sp1. Our present results implicate the newly indentified miR-22/Sp1/PTEN/AKT axis might represent a potential therapeutic target for colorectal cancer.

摘要

微小RNA最近已成为包括细胞增殖、发育和分化在内的许多生物学过程的调节因子。本研究发现,在结直肠癌临床标本和高转移细胞系中,miR-22在统计学上有所降低。此外,低miR-22表达与肿瘤转移、临床晚期和复发相关。与临床观察结果一致,miR-22在体外和体内均显著抑制结直肠癌细胞的生长和转移能力。Sp1被验证为miR-22的靶标,Sp1的异位表达削弱了miR-22的抑制作用。此外,Sp1通过与miR-22启动子结合来抑制miR-22转录,从而形成负反馈回路。进一步研究表明,miR-22通过Sp1抑制PTEN/AKT通路的活性。我们目前的结果表明,新发现的miR-22/Sp1/PTEN/AKT轴可能代表结直肠癌的一个潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5a/5482653/df715e02ad35/oncotarget-08-36266-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5a/5482653/b233aca26e8b/oncotarget-08-36266-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5a/5482653/c3cac0cb1b46/oncotarget-08-36266-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5a/5482653/82f1937a68c5/oncotarget-08-36266-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5a/5482653/9804b49ae483/oncotarget-08-36266-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5a/5482653/549fa9e80dc1/oncotarget-08-36266-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5a/5482653/d918b442006d/oncotarget-08-36266-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5a/5482653/a852a879e0ca/oncotarget-08-36266-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5a/5482653/df715e02ad35/oncotarget-08-36266-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5a/5482653/b233aca26e8b/oncotarget-08-36266-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5a/5482653/c3cac0cb1b46/oncotarget-08-36266-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5a/5482653/82f1937a68c5/oncotarget-08-36266-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5a/5482653/9804b49ae483/oncotarget-08-36266-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5a/5482653/549fa9e80dc1/oncotarget-08-36266-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5a/5482653/d918b442006d/oncotarget-08-36266-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5a/5482653/a852a879e0ca/oncotarget-08-36266-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5a/5482653/df715e02ad35/oncotarget-08-36266-g008.jpg

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