Tumor suppressor PLZF regulated by lncRNA ANRIL suppresses proliferation and epithelial mesenchymal transformation of gastric cancer cells

Abstract

Promyelocytic leukemia zinc finger (PLZF) plays important roles in tumorigenic and developmental processes of various types of cancers. However, the expression of PLZF in gastric cancer (GC) has not been reported. The aim of the present study was to investigate the expression level and potential status of PLZF in GC as well as its possible mechanism. In the present study, we found that PLZF was downregulated in the majority of GC cell lines and tumor tissues and that alteration of PLZF expression was closely correlated with a malignant phenotype, epithelial-mesenchymal transformation and overall survival. Evaluation of in vitro proliferation, colony information, migration and invasion indicated that PLZF gene transduction induced a less malignant phenotype, which was also confirmed through in vivo studies performed in athymic nude mice. Furthermore, we assessed the expression levels of the lncRNA ANRIL in GC and found that it was negatively associated with the level of PLZF and that ANRIL indirectly methylated PLZF to suppress its expression via binding with polycomb repressive complex 2. When GC cells were treated with the methylation inhibitor 5-Aza-2'-deoxycytidine, the expression of PLZF increased, which further confirmed that PLZF was methylated. These results indicated that constitutive ANRIL activation was a possible cause of the lack of PLZF expression in GC cells. Coupled deregulation of PLZF and ANRIL may account for most of the alterations described in GC, and PLZF may become a potential target of GC therapy.

The control of polycomb repressive complexes by long noncoding RNAs

“…A detailed discussion of each lncRNA is beyond the scope of this review (Amandio et al, 2016; d'Ydewalle et al, 2017; Gupta et al, 2010; Holdt et al, 2013; Huarte et al, 2010; Jia et al, 2016; Jin et al, 2018; Kang et al, 2020; Klattenhoff et al, 2013; Kotake et al, 2011; Kotzin et al, 2016; L. Li et al, 2013; G. Y. Liu et al, 2016; Maamar et al, 2013; Marin‐Bejar et al, 2013, 2017; Negishi et al, 2014; Pasmant et al, 2007; Portoso et al, 2017; M. K. Ray et al, 2016; Rinn et al, 2007; Schorderet & Duboule, 2011; Tsai et al, 2010; J. B. Wang, Jin, et al, 2019; Woo et al, 2017; Yap et al, 2010; Yin et al, 2015; J. Yu et al, 2020; W. Yu et al, 2008; K. J. Zhang et al, 2020; Zhou et al, 2015; Zhu & Xu, 2013). However, key aspects of each lncRNA, as well as relevant references, are summarized in Table S1.…”

Regulating of cell cycle progression by the lncRNA CDKN2B-AS1/miR-324-5p/ROCK1 axis in laryngeal squamous cell cancer

“…lncRNA ANRIL (CDKN2B-AS1) is an antisense of the cyclin-dependent kinase inhibitor 2B (CDKN2B), which plays important roles in coronary artery disease, ischemic stroke, chronic obstructive pulmonary disease, inflammatory regulation, and various cancers. [7][8][9][10][11] Several miRNAs have been identified as targets of CDKN2B-AS1. For example, in glioma cells, CDKN2B-AS1 could promote cell growth, migration, and invasion by regulating miR-34a.…”

Interaction of ncRNA and Epigenetic Modifications in Gastric Cancer: Focus on Histone Modification

“…This lncRNA recruits EZH2, a core member of PRC2, in turn catalyzes H3K27 trimethylation, which then drives PLZF gene silencing by increasing DNA methylation of PLZF. In summary, lncRNA ANRIL suppresses EMT as well as cell proliferation through epigenetic regulation of the tumor suppressor PLZF (114).…”