Downregulated USP3 mRNA functions as a competitive endogenous RNA of SMAD4 by sponging miR-224 and promotes metastasis in colorectal cancer

被引：37

作者：

Wang, Zaozao ^{[1
]}

Yang, Jie ^{[1
]}

Di, Jiabo ^{[1
]}

Cui, Ming ^{[1
]}

Xing, Jiadi ^{[1
]}

Wu, Fan ^{[1
]}

Wu, Wei ^{[1
]}

Yang, Hong ^{[1
]}

Zhang, Chenghai ^{[1
]}

Yao, Zhendan ^{[1
]}

Zhang, Nan ^{[1
]}

Jiang, Beihai ^{[1
]}

Su, Xiangqian ^{[1
]}

机构：

[1] Peking Univ, Canc Hosp & Inst, Dept Gastrointestinal Surg 4, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing 100142, Peoples R China

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

基金：

中国国家自然科学基金; 北京市自然科学基金; 国家高技术研究发展计划(863计划);

关键词：

CELL-PROLIFERATION; TGF-BETA; MICRORNAS; 5-FLUOROURACIL; PROGRESSION; RESISTANCE; NETWORKS; PATHWAYS; ORIGINS; MARKER;

D O I：

10.1038/s41598-017-04368-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Increasing evidence shows that competitive endogenous RNAs (ceRNAs) can affect the expression of other transcripts by sequestering common microRNAs (miRNAs), and participate in tumourigenesis. As a potent tumour suppressor in colorectal cancer (CRC), SMAD4 is regulated by many miRNAs. However, the regulation of SMAD4 by ceRNAs has never been examined. In the present study, we found that USP3 modulated SMAD4 expression in a miRNA dependent, and protein-coding gene independent manner. USP3 and SMAD4 were directly targeted by miR-224, and overexpression of the USP3 3'UTR could inhibit metastasis caused by the loss of USP3. The correlation of USP3, SMAD4 and miR-224 expression was further verified in CRC specimens. Additionally, the loss of USP3 was associated with distal metastasis and a poor prognosis. Altogether, our study demonstrates USP3 as a bona fide SMAD4 ceRNA. The results from this study may provide new insights into the prevention and treatment of CRC.

引用

页数：14

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[1] MicroRNAs as novel targets and tools in cancer therapy [J].