Downregulated USP3 mRNA functions as a competitive endogenous RNA of SMAD4 by sponging miR-224 and promotes metastasis in colorectal cancer
Abstract 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. Howev...
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2017
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oai:doaj.org-article:2a40c987966d4266861a1cfe6952d3c02021-12-02T16:06:49ZDownregulated USP3 mRNA functions as a competitive endogenous RNA of SMAD4 by sponging miR-224 and promotes metastasis in colorectal cancer10.1038/s41598-017-04368-32045-2322https://doaj.org/article/2a40c987966d4266861a1cfe6952d3c02017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04368-3https://doaj.org/toc/2045-2322Abstract 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.Zaozao WangJie YangJiabo DiMing CuiJiadi XingFan WuWei WuHong YangChenghai ZhangZhendan YaoNan ZhangBeihai JiangXiangqian SuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) |
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Medicine R Science Q Zaozao Wang Jie Yang Jiabo Di Ming Cui Jiadi Xing Fan Wu Wei Wu Hong Yang Chenghai Zhang Zhendan Yao Nan Zhang Beihai Jiang Xiangqian Su Downregulated USP3 mRNA functions as a competitive endogenous RNA of SMAD4 by sponging miR-224 and promotes metastasis in colorectal cancer |
| description |
Abstract 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. |
| format |
article |
| author |
Zaozao Wang Jie Yang Jiabo Di Ming Cui Jiadi Xing Fan Wu Wei Wu Hong Yang Chenghai Zhang Zhendan Yao Nan Zhang Beihai Jiang Xiangqian Su |
| author_facet |
Zaozao Wang Jie Yang Jiabo Di Ming Cui Jiadi Xing Fan Wu Wei Wu Hong Yang Chenghai Zhang Zhendan Yao Nan Zhang Beihai Jiang Xiangqian Su |
| author_sort |
Zaozao Wang |
| title |
Downregulated USP3 mRNA functions as a competitive endogenous RNA of SMAD4 by sponging miR-224 and promotes metastasis in colorectal cancer |
| title_short |
Downregulated USP3 mRNA functions as a competitive endogenous RNA of SMAD4 by sponging miR-224 and promotes metastasis in colorectal cancer |
| title_full |
Downregulated USP3 mRNA functions as a competitive endogenous RNA of SMAD4 by sponging miR-224 and promotes metastasis in colorectal cancer |
| title_fullStr |
Downregulated USP3 mRNA functions as a competitive endogenous RNA of SMAD4 by sponging miR-224 and promotes metastasis in colorectal cancer |
| title_full_unstemmed |
Downregulated USP3 mRNA functions as a competitive endogenous RNA of SMAD4 by sponging miR-224 and promotes metastasis in colorectal cancer |
| title_sort |
downregulated usp3 mrna functions as a competitive endogenous rna of smad4 by sponging mir-224 and promotes metastasis in colorectal cancer |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/2a40c987966d4266861a1cfe6952d3c0 |
| work_keys_str_mv |
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1718384831107170304 |