Figure 4.

The proposed mechanisms of NEAT1 action in cancer. The diagram illustrates signaling events upstream and downstream of NEAT1 in cancer. The EGFR-STAT3/NF-κB signaling pathway is a critical triggering mechanism upstream of NEAT1, which inhibits cell cycle arrest and apoptosis, but promotes migration, invasion, metastasis, epithelial-to-mesenchymal transition, stem cell-like phenotype, chemoresistance and radioresistance, through at least three major mechanisms: (i) NEAT1 functions as a scaffold RNA molecule by interacting with EZH2 (a subunit of the polycomb repressive complex) to influence the expression of downstream effectors of EZH2, (ii) NEAT1 acts as a miRNA sponge to antagonize the interactions between multiple tumor suppressor miRNAs and target mRNAs, and (iii) NEAT1 suppresses the expression of miR-129 by promoting the DNA methylation of the miR-129 promoter.