MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4.
MicroRNA-20a-5p promotes colorectal cancer invasion and metastasis by downregulating Smad4.
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DOI：
10.18632/oncotarget.9900
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发表时间：
2016-07-19
期刊：
影响因子：
--
通讯作者：
Peng Z
中科院分区：
文献类型：
--
作者：
Cheng D;Zhao S;Tang H;Zhang D;Sun H;Yu F;Jiang W;Yue B;Wang J;Zhang M;Yu Y;Liu X;Sun X;Zhou Z;Qin X;Zhang X;Yan D;Wen Y;Peng Z
肿瘤转移是导致结直肠癌患者预后不良的主要原因之一。Smad4的缺失有助于许多人类癌症的侵袭过程。然而，Smad4异常表达在结直肠癌发展中的潜在精确机制仍然知之甚少。miR-20a-5p通过直接靶向Smad4在人结直肠癌细胞中的3'UTR负调控Smad4。miR-20a-5p不仅在体外促进CRC细胞的侵袭能力和体内肝脏转移，而且通过下调Smad4的表达，促进了上皮细胞向间质细胞的转化过程。此外，从544例CRC患者临床特征中获得的组织微阵列分析显示，miR-20a-5p在人CRC组织中表达上调，尤其是在有转移的组织中。高水平miR-20a-5p预示CRC患者预后不良。应用5个miRNA靶标预测程序来鉴定CRC中Smad4靶标的潜在miRNA。采用荧光素酶报告基因检测和转染技术验证CRC中miR-20a-5p与Smad4的相关性。在体外和体内实验中，采用伤口愈合、transwell和肿瘤发生实验来探索miR-20a-5p和Smad4在CRC进展中的功能。基于组织微阵列数据，通过Kaplan-Meier分析和多变量cox比例风险分析评估miR-20a-5p表达与CRC患者预后的关系。miR-20a-5p作为一种onco-miRNA，通过抑制结直肠癌细胞中Smad4的表达来促进其侵袭和转移能力，高水平的miR-20a-5p预测结直肠癌患者预后不良，为人类结直肠癌提供了一个新的有前景的治疗靶点。
Tumor metastasis is one of the leading causes of poor prognosis for colorectal cancer (CRC) patients. Loss of Smad4 contributes to aggression process in many human cancers. However, the underlying precise mechanism of aberrant Smad4 expression in CRC development is still little known. miR-20a-5p negatively regulated Smad4 by directly targeting its 3′UTR in human colorectal cancer cells. miR-20a-5p not only promoted CRC cells aggression capacity in vitro and liver metastasis in vivo, but also promoted the epithelial-to-mesenchymal transition process by downregulating Smad4 expression. In addition, tissue microarray analysis obtained from 544 CRC patients’ clinical characters showed that miR-20a-5p was upregulated in human CRC tissues, especially in the tissues with metastasis. High level of miR-20a-5p predicted poor prognosis in CRC patients. Five miRNA target prediction programs were applied to identify potential miRNA(s) that target(s) Smad4 in CRC. Luciferase reporter assay and transfection technique were used to validate the correlation between miR-20a-5p and Smad4 in CRC. Wound healing, transwell and tumorigenesis assays were used to explore the function of miR-20a-5p and Smad4 in CRC progression in vitro and in vivo. The association between miR-20a-5p expression and the prognosis of CRC patients was evaluated by Kaplan–Meier analysis and multivariate cox proportional hazard analyses based on tissue microarray data. miR-20a-5p, as an onco-miRNA, promoted the invasion and metastasis ability by suppressing Smad4 expression in CRC cells, and high miR-20a-5p predicted poor prognosis for CRC patients, providing a novel and promising therapeutic target in human colorectal cancer.
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影响因子：
11.2
作者：
Papageorgis P;Cheng K;Ozturk S;Gong Y;Lambert AW;Abdolmaleky HM;Zhou JR;Thiagalingam S
通讯作者：
Thiagalingam S
影响因子：
8.8
作者：
Miyo M;Yamamoto H;Konno M;Colvin H;Nishida N;Koseki J;Kawamoto K;Ogawa H;Hamabe A;Uemura M;Nishimura J;Hata T;Takemasa I;Mizushima T;Doki Y;Mori M;Ishii H
通讯作者：
Ishii H
影响因子：
10.1
作者：
Jiang H;Wang P;Li X;Wang Q;Deng ZB;Zhuang X;Mu J;Zhang L;Wang B;Yan J;Miller D;Zhang HG
通讯作者：
Zhang HG
影响因子：
11.2
作者：
Li Y;Kuscu C;Banach A;Zhang Q;Pulkoski-Gross A;Kim D;Liu J;Roth E;Li E;Shroyer KR;Denoya PI;Zhu X;Chen L;Cao J
通讯作者：
Cao J
DOI：
10.1158/1541-7786.mcr-14-0192-t
发表时间：
2014-08
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Park JW;Jang SH;Park DM;Lim NJ;Deng C;Kim DY;Green JE;Kim HK
通讯作者：
Kim HK