miR-6716-5p promotes metastasis of colorectal cancer through downregulating NAT10 expression

Zhenzhen Liu; Xiaofeng Liu; Yuan Li; Pengwei Ren; Chunfeng Zhang; Lijun Wang; Xiaojuan Du; Baocai Xing

doi:10.2147/CMAR.S197733

miR-6716-5p promotes metastasis of colorectal cancer through downregulating NAT10 expression

Cancer Manag Res. 2019 Jun 6:11:5317-5332. doi: 10.2147/CMAR.S197733. eCollection 2019.

Authors

Zhenzhen Liu¹, Xiaofeng Liu¹, Yuan Li¹, Pengwei Ren², Chunfeng Zhang³, Lijun Wang¹, Xiaojuan Du², Baocai Xing¹

Affiliations

¹ Hepatopancreatobiliary Surgery Department I, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University School of Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, People's Republic of China.
² Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, People's Republic of China.
³ Department of Medical Genetics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, People's Republic of China.

Abstract

Background: Human N-acetyltransferase 10 (NAT10) plays pivotal roles in cellular biological processes, such as senescence, autophagy and cytokinesis. The expression of NAT10 is dysregulated in colorectal cancer (CRC) and is associated with the prognosis of patients. However, it remains unclear how NAT10 is regulated in CRC. Methods: The microRNA(miRNA) regulating NAT10 was predicted by bioinformatics analysis and further validated by real-time quantitative PCR(RT-qPCR),Western blot and dual luciferase reporter assays. The expression of the miRNA regulating NAT10 in CRC tissues was examined using RT-qPCR. Cell proliferation, cell apoptosis, cell migration and cell invasion assays were performed after transfection with miRNA mimic and inhibitor. Results: Here, we report that miR-6716-5p inhibits the expression of NAT10 in CRC. The NAT10 protein level was downregulated by the miR-6716-5p mimic, and was upregulated by the miR-6716-5p inhibitor in CRC cell lines. In addition, miR-6716-5p bound to the 3'-untranslated region of NAT10 mRNA and decreased NAT10 mRNA levels. Significantly, the miR-6716-5p level was higher in the tumor tissues of the CRC patients with liver metastasis than that in the non-metastatic CRC patients. In addition, the miR-6716-5p level was correlated with poor overall survival of CRC patients with liver metastasis. The miR-6716-5p inhibitor inhibited CRC cell migration and invasion. Consistently, the miR-6716-5p mimic significantly promoted cell migration and invasion, and this effect is dependent on NAT10. However, miR-6716-5p had no effect on CRC cell proliferation and apoptosis. We found that miR-6716-5p negatively regulated E-cadherin protein levels. In addition, E-cadherin was upregulated by NAT10 in CRC cells, confirming that miR-6716-5p downregulated E-cadherin levels by inhibiting NAT10 expression. Conclusion: We demonstrated that miR-6716-5p acts as a crucial regulator of NAT10 to promote cell migration and invasion in CRC by inhibiting NAT10 expression. Our data suggest that miR-6716-5p/NAT10 might act as a potential therapeutic target for CRC treatment.

Keywords: NAT10; colorectal cancer; CRC; liver metastasis; miR-6716-5p.