POLR3G, encoding RNA Polymerase III Subunit G, is a key component of RNA polymerase III, which transcribes short untranslated RNAs involved in gene expression regulation [2,5,8]. Two isoforms of human Pol III exist, differentiated by the presence of POLR3G/RPC32α or POLR3GL/RPC32β subunits [2]. POLR3G is expressed in embryonic stem cells and certain transformed cells, with its expression potentially regulated by a gene-internal super-enhancer and multiple transcription factors [2,5].

In cancer research, POLR3G has shown oncogenic effects. In triple-negative breast cancer (TNBC), POLR3G KO in MDA-MB231 cells reduces anchorage-independent growth, invasive capabilities in vitro, and impairs tumor growth and metastasis in orthotopic xenografts in mice [2]. In bladder cancer, POLR3G deficiency leads to reduced migration and invasion of cells both in vitro and in vivo, and it promotes epithelial-mesenchymal transition (EMT) through activation of the PI3K/AKT signaling pathway [1,6]. In lung cancer, miR-26a-5p, which directly regulates POLR3G expression, can suppress cancer stemness and increase chemosensitivity [3]. In transitional cell carcinoma, POLR3G is up-regulated, and high expression correlates with poor prognosis, with gene set enrichment analysis showing enrichment of tumor-related pathways like TGF-β, PI3K-AKT-mTOR, and IL6-JAK-STAT3 signaling [4].

In conclusion, POLR3G plays a crucial role in cancer development, influencing tumor growth, metastasis, and EMT, as revealed by gene knockout models in various cancer types. These findings suggest POLR3G could be a potential prognostic biomarker and therapeutic target in multiple cancers. Additionally, in mouse development, POLR3G knockout mice die at an early embryonic stage, highlighting its importance in this context [7].