EZH2: A Crucial Competing Endogenous RNA in Cancer Research-A Scoping Review

Recently, research on the competing endogenous RNAs (ceRNAs) in cancer has been in full swing, emphasizing their importance as critical RNAs in cancer progression. Enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) is a ceRNA that has been introduced as a potential therapeutic target in many cancers. Due to EZH2's dual role as an oncogene and tumor suppressor in cancer, a more thorough exploration of its ceRNA functions may enhance clinical cancer treatment approaches. In the current scoping review, we searched several online databases to identify experimentally validated ceRNA axes, including EZH2 in human cancers. We identified 66 unique axes consisting of 30 microRNAs (miRNAs), 32 long non-coding RNAs (lncRNAs), 9 messenger RNAs (mRNAs), and 14 circular RNAs (circRNAs). Notably, SPRY4-IT1 - miR-101-3p - EZH2 and XIST - miR-101-3p - EZH2 were recurrent axes observed in multiple cancer types. Among the most frequent miRNAs were miR-101-3p, miR-144-3p and miR-124-3p, and ceRNAs including SPRY4-IT1, XIST, SNHG6, HOXA11-AS, MALAT1, and TUG1 emerged as frequent competitors of EZH2 for miRNA binding. This scoping review highlights the diversity of EZH2-containing ceRNA axes in cancer, suggesting their potential as therapeutic targets. Further studies are needed to clarify their roles and clinical utility.