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Cancer Lett. 2017 Dec 1;410:158-168. doi: 10.1016/j.canlet.2017.09.026. Epub 2017 Sep 28.

NUDT21 regulates 3'-UTR length and microRNA-mediated gene silencing in hepatocellular carcinoma.

Author information

1
Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, Hunan, China. Electronic address: 351518959@qq.com.
2
Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, Hunan, China. Electronic address: 463341750@qq.com.
3
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University (ECNU), Shanghai 200241, China. Electronic address: dlli@bio.ecnu.edu.cn.
4
The Third Xiangya Hospital of Central South University, Changsha 410013, Hunan, China. Electronic address: ygp9880@163.com.
5
Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, Hunan, China. Electronic address: chengzn@csu.edu.cn.
6
Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, Hunan, China. Electronic address: biqbz@hotmail.com.

Abstract

Recent studies have shown that several microRNAs (miRNAs) are involved in hepatocellular carcinoma (HCC) tumorigenesis and metastasis; however, the mechanisms responsible for the differences in the functions of these miRNAs in liver cancer remain a mystery. In our previous study, we identified NUDT21 as an interaction partner of argonaute 2 (AGO2). NUDT21 has been reported to be involved in alternative polyadenylation (APA); thus, the interaction between NUDT21 and AGO2 may be a key component of the crosstalk between APA and miRNA-mediated gene silencing in HCC. Our data showed that NUDT21 expression was decreased in HCC. Moreover, our results showed that NUDT21 co-localized with AGO2 in P/GW bodies in normal liver cells; however, this co-localization was diminished in cancer cells. Functional studies showed that NUDT21 elongated the 3'-UTR of mRNA and enhanced the efficiency of miRNA-mediated gene silencing by increasing the efficiency of AGO2-mRNA binding, which played an important role in cell proliferation. In summary, loss of NUDT21 shortened the 3'-UTR of various oncogenes in HCC cells. The shorter 3'-UTR contained less miRNA binding sites, which enabled the oncogenes to evade miRNA regulation and become overexpressed in HCC, leading to unregulated cancer cell proliferation.

KEYWORDS:

Alternative polyadenylation; Hepatocellular carcinoma; NUDT21; RNA-induced silencing complex; microRNA

PMID:
28964783
DOI:
10.1016/j.canlet.2017.09.026
[Indexed for MEDLINE]

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