Inhibitory Effect of TRIM22 Overexpression on the Proliferation of Hepatocellular Carcinoma through CREB1 Degradation
Abstract
Li Yong, Wu Bin, Dawei Deng, Guangnian Zhang, Chen Chang, Junfeng Song, Jianxiong Jing, and Deng Yi
Tripartite motif-containing 22 (TRIM22) belongs to the extensive tripartite motif (TRIM) protein family, hypothesized to act as a tumor suppressor among various malignancies. However, its definitive role as well as clinical implications in hepatocellular carcinoma (HCC) have remained unclear. Our preliminary findings suggest frequent downregulation of TRIM22 expression in primary HCC samples. Conversely, we observed a favorable prognosis associated with overexpression of TRIM22. Rigorous experimentation revealed that elevated levels of TRIM22 significantly restricted the proliferation potential of HCC. Upon delv- ing into the mechanistic intricacies, we identified a direct interaction between TRIM22 and cAMP response element-binding protein 1 (CREB1), a pivotal player in cancer growth regulation. In the presence of TRIM22, CREB1 undergoes ubiquitination and subsequent degradation, inhibiting the expression of CREB1-related genes in HCC. Importantly, the inhibitory effect of TRIM22 on HCC proliferation was dependent on CREB1 degradation. Therefore, for the first time, the present study proved the crucial anti-tumor role of TRIM22 in HCC tumorigenesis and highlighted its potential as a prognostic and therapeutic target in the treatment of HCC.