Review Article: YY2 in Tumor Regulation: Core Mechanisms and Functional Networks

Ying Yang 2 (YY2), a member of the Yin Yang (YY) transcription factor family characterized by C2H2-type zinc finger domains, has emerged as a pivotal yet paradoxical regulator in tumor biology. While structurally homologous to YY1, YY2 exhibits context-dependent dual roles in different cancers: in hepatocellular carcinoma (HCC), it functions as a tumor suppressor by directly inhibit cholesterol synthesis; whereas in esophageal carcinoma, YY2 acts as an oncogenic facilitator by upregulating the expression of key glycolytic genes PDHA1/PDK3, thereby promoting metabolic reprogramming of tumor cells. This review systematically synthesizes current understanding of YY2 multifaceted roles in metabolic reprogramming regulation, cancer stem cell maintenance, ensuring chromosomal stability, and remodeling tumor immune microenvironment. We particularly highlight YY2 functional duality-its ability to suppress tumor initiation while paradoxically promoting therapy resistance in advanced cancers. Collectively, these findings position YY2 as a key multifaceted transcriptional regulator linking metabolic pathways, genomic stability, and immune responses in cancer cells.