RNF180, an E3 ubiquitin ligase, is a tumor suppressor gene. It is involved in multiple cellular processes such as cell development, proliferation, and apoptosis. RNF180 participates in pathways like regulating STAT3 activity via RhoC proteasomal degradation in gastric cancer cells, and is also related to the ubiquitination-degradation of proteins like WISP1 in colorectal cancer, DNMT1 in gastric cancer, and RAD51 in triple-negative breast cancer [2,4,5,6].

In colorectal cancer, overexpression of RNF180 inhibits cell viability and promotes apoptosis, while its depletion enhances cell survival, with WISP1 being a critical downstream molecule [2]. In gastric cancer, RNF180 overexpression can suppress STAT3 phosphorylation, and it can also prevent excessive PCDH10 methylation by promoting DNMT1 ubiquitination, thus suppressing cell proliferation and metastasis [4,5]. In triple-negative breast cancer, RNF180 degrades RAD51 by ubiquitination, inhibiting cell growth, metastasis, and reducing gefitinib resistance [6]. Plasma RNF180 gene methylation shows a relatively high diagnostic value for gastric cancer, with combined sensitivity of 0.54 and specificity of 0.80 according to a meta-analysis, and may serve as a non-invasive biomarker [1,3].

In conclusion, RNF180 is a crucial tumor suppressor gene involved in regulating cell proliferation, apoptosis, and metastasis in various cancers, especially gastric and colorectal cancers. Studies on RNF180, including those using loss-of-function models in cell lines, have revealed its key role in these biological processes and its potential as a diagnostic biomarker and therapeutic target in cancer [2-5,7,8].