Unknown

Dataset Information

0

EZH2-DNMT1-mediated epigenetic silencing of miR-142-3p promotes metastasis through targeting ZEB2 in nasopharyngeal carcinoma.


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.

SUBMITTER: Li Y 

PROVIDER: S-EPMC6748116 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

EZH2-DNMT1-mediated epigenetic silencing of miR-142-3p promotes metastasis through targeting ZEB2 in nasopharyngeal carcinoma.

Li Yingqin Y   He Qingmei Q   Wen Xin X   Hong Xiaohong X   Yang Xiaojing X   Tang Xinran X   Zhang Panpan P   Lei Yuan Y   Sun Ying Y   Zhang Jian J   Wang Yaqin Y   Ma Jun J   Liu Na N  

Cell death and differentiation 20181023 6


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 an  ...[more]

Similar Datasets

| S-EPMC7392008 | biostudies-literature
| S-EPMC10416723 | biostudies-literature
| S-EPMC4742098 | biostudies-literature
| S-EPMC8040730 | biostudies-literature
| S-EPMC7408254 | biostudies-literature
| S-EPMC5629759 | biostudies-literature
| S-EPMC6792493 | biostudies-literature
| S-EPMC6111854 | biostudies-other
| S-EPMC3943182 | biostudies-other
| S-EPMC4323870 | biostudies-literature