Non-coding RNAs-EZH2 regulatory mechanisms in cervical cancer: The current state of knowledge

Cervical cancer (CC) is among the leading causes of death in women worldwide. Both genetic and epigenetic regulators are required for the tumorigenesis and progression of CC. Non-coding RNAs (ncRNAs) are a group of RNAs that don't code for proteins yet constitute a large part of the human transcriptome, including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), circular RNAs (circRNA), and other forms of non-coding RNAs. Deregulation of lncRNA, miRNA, and circRNA is implicated in the oncogenesis and development of cervical malignancies, acting as oncogenic drivers or tumor suppressors. Enhancer of zeste homolog 2 (EZH2) is the enzymatic subunit of Polycomb Repressive Complex 2 (PRC2), which functions to methylate histone H3 lysine 27 to silence gene transcription. Converging lines of evidence have revealed the oncogenic role played by EZH2 in cancers. EZH2 is upregulated in CC tissues with a robust correlation to the advanced stage, metastasis, and poor survival rate in patients. The elucidation of the roles of EZH2 in cancer has driven the development of therapeutic EZH2 inhibitors, which are approaching phase I or phase I/II clinical trials. Here we review the ncRNA-EZH2 regulatory pathways in CC that unify EZH2 and ncRNAs as an integrated system in the development of CC. Given the emerging findings for the role of the ncRNA-EZH2 regulatory axis in CC, it will be of great interest to develop novel therapeutic strategies based on their relationship.