EZH2-DNMT1-mediated Epigenetic Silencing of MiR-142-3p Promotes Metastasis Through Targeting ZEB2 in Nasopharyngeal Carcinoma

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2018 Oct 25

PMID 30353102

Citations 38

Authors

Yingqin Li

Qingmei He

Xin Wen

Xiaohong Hong

Xiaojing Yang

Xinran Tang

Panpan Zhang

Yuan Lei

Ying Sun

Jian Zhang

Yaqin Wang

Jun Ma

Na Liu

Affiliations

Soon will be listed here.

Abstract

Human nasopharyngeal carcinoma (NPC) has the highest metastatic rate in head and neck. However, the mechanisms underlying NPC metastasis remain unclear. Here using propensity-score-matched miRNA microarray analysis, miR-142-3p is identified to be the most correlated with distant-metastasis-free survival and downregulated in paraffin-embedded NPC with distant metastasis, which is validated in both internal cohort and external GEO dataset from Canada. miR-142 locus hypermethylation was observed and found to be associated with miR-142-3p downregulation in metastatic NPC. Furthermore, miR-142-3p was epigenetically silenced by EZH2-recruited DNMT1 and suppressed NPC cell metastasis and EMT. Intersecting PCR array gene profiling with bioinformatic prediction, we identify ZEB2 as a direct and functional target of miR-142-3p in NPC. Reversal of miR-142-3p silencing efficiently suppresses NPC cell invasion and metastasis. Moreover, epigenetic miR-142 hypermethylation is correlated with unfavorable prognosis in both training and validation cohorts. This study identifies miR-142-3p as a key suppressive regulator in NPC metastasis and reveals a DNMT1-mediated epigenetic mechanism for miR-142-3p silencing, providing a potential prognostic marker and therapeutic target to combat NPC metastasis.

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