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]. There are two isoforms of human Pol III, with POLR3G or its paralog POLR3GL, showing differential expression patterns [2,7,8]. POLR3G is expressed in embryonic stem cells and certain transformed cells, while POLR3GL is ubiquitously expressed [2,7].

In cancer research, POLR3G has emerged as a significant factor. 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 reduces cell migration and invasion both in vitro and in vivo, and downregulates EMT-related mesenchymal markers, with POLR3G acting through the PI3K/AKT signaling pathway [1]. 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 such as TGF-β, PI3K-AKT-mTOR, and IL6-JAK-STAT3 signaling [4]. In a bladder cancer rat model, POLR3G expression increases during cancer development, and knockdown in cell lines inhibits proliferation, migration, and invasion, with involvement in the Wnt signaling pathway [6].

In conclusion, POLR3G plays crucial roles in cancer-related biological processes such as tumorigenesis, metastasis, EMT, and cancer stemness. Gene knockout models, especially in the context of cancer research, have been instrumental in revealing its functions and associated signaling pathways, highlighting its potential as a prognostic biomarker and therapeutic target in multiple cancer types [1,2,3,4,6].