Oncotarget

Research Papers:

MiR-486-5p negatively regulates oncogenic NEK2 in hepatocellular carcinoma

Shun-Jun Fu, Jian Chen, Fei Ji, Wei-Qiang Ju, Qiang Zhao, Mao-Gen Chen, Zhi-Yong Guo, Lin-Wei Wu, Yi Ma, Dong-Ping Wang, Xiao-Feng Zhu and Xiao-Shun He _

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Oncotarget. 2017; 8:52948-52959. https://doi.org/10.18632/oncotarget.17635

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Abstract

Shun-Jun Fu1,2,3, Jian Chen1,2,3, Fei Ji1,2,3, Wei-Qiang Ju1,2,3, Qiang Zhao1,2,3, Mao-Gen Chen1,2,3, Zhi-Yong Guo1,2,3, Lin-Wei Wu1,2,3, Yi Ma1,2,3, Dong-Ping Wang1,2,3, Xiao-Feng Zhu1,2,3 and Xiao-Shun He1,2,3

1Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China

2Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China

3Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, P. R. China

Correspondence to:

Xiao-Shun He, email: gdtrc@163.com

Keywords: NEK2, MiR-486-5p, hepatocellular carcinoma, tumor progression, prognosis

Received: September 27, 2016    Accepted: March 10, 2017    Published: May 05, 2017

ABSTRACT

NEK2 is a member of the NIMA-related family of serine/threonine centrosomal kinases. We analyzed the relationship between differential expression of NEK2 and hepatocellular carcinoma (HCC) patient outcomes after liver transplants. We also studied the microRNAs that affect NEK2 expression. Analysis of multiple microarrays in the Oncomine database revealed that NEK2 expression was higher in HCC tissues than adjacent normal liver tissues. High NEK2 expression correlated with tumor size, pathological grade and macro- and microvascular invasion. Consequently, patients exhibiting high NEK2 expression had poorer prognosis. This was corroborated by our multivariate analysis that showed NEK2 to be an independent prognostic factor for HCC patient survival. Further, high NEK2 expression promoted proliferation, colony formation, migration and invasion of HCC cell lines. Tumor xenograft data from Balb/c nude mice demonstrated that HCC cells with high NEK2 expression formed larger tumors than those with low NEK2 expression. Finally, we showed that miR-486-5p suppressed NEK2 by directly binding to its transcript 3’UTR. We also demonstrated an inverse relationship between miR-486-5p and NEK2 expression in HCC patients. These findings suggest miR-486-5p negatively regulates NEK2, which is a critical prognostic indicator of HCC patient survival after liver transplantation.


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