ZNF452 facilitates tumor proliferation and invasion via activating AKT-GSK3β signaling pathway and predicts poor prognosis of non-small cell lung cancer patients

Abstract

ZNF452 is a zinc-finger protein family member which contains an isolated SCAN (SRE-ZBP, CTfin51, AW-1 and Number 18 cDNA) zinc-finger domain. Despite the SCAN N-terminus domain is known to play a role in transcriptional regulation of genes involved in cell survival and differentiation, there are no precise cellular functions that have been assigned to ZNF452. In the present study, we found that either endogenous or exogenous ZNF452 was overexpressed in the cytoplasm of NSCLC cells and positive ratio of ZNF452 in NSCLC samples (50.8%, 93/183) was significantly higher than that in normal lung tissues (22.4%, 13/58, P<0.001). ZNF452 overexpression was correlated with advanced TNM stage (P=0.033), positive lymph node metastasis (P=0.002) and predicted poor overall survival of NSCLC patients (P<0.001). ZNF452 facilitated tumor growth, colony formation, G1-S phase arrest, migration and invasion through upregulating the levels of CyclinD1, CyclinE1, p-Rb, or Snail, and downregulating the expression of Zo-1. In nude mice xenografts, overexpressing ZNF452 also promoted tumor proliferation and metastasis. Subsequently, we found that the effect of ZNF452 on facilitating tumor proliferation and invasion was through activating its downstream AKT-GSK3β signaling pathway. Treatment of AKT inhibitor markedly prevented the phosphorylation of AKT and GSK3β which subsequently counteracted increasing expression of CyclinD1, CyclinE1 or Snail and restored the decreasing expression of Zo-1, as well as the upregulation of tumor proliferation and invasion, caused by ZNF452 overexpression.Taken together, the present study indicated that ZNF452 may be an upstream regulator of AKT-GSK3β signaling pathway and facilitates proliferation and invasion of NSCLC.

A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation

“…While cg09249800 was the most statistically significant association, its effect size (−2.8 × 10 −3 ) was nearly 4 times smaller than strongest effect size CpG which was cg26865747, (coefficient = 0.0105), proximal to the SCAND3 gene, a zinc finger transcription factor implicated in tumor proliferation and invasion 44 . Significant individual CpG sites ranged in effect sizes from 0.0001 to 0.01, namely over two orders of magnitude, and 70 of the 341 CpGs had larger effect sizes than the most significant single CpG site at ACOT7 .…”