CCDC43 as a potential therapeutic target of Tian Yang Wan for the treatment of hepatocellular carcinoma by activating the hippo pathway.

Introduction: Hepatocellular carcinoma (HCC) prevalence is rising annually, but the existing treatment strategies are limited; therefore, it is crucial to explore new therapeutic approaches. Methods: Here, we investigate the potential anti-cancer mechanism of an herbal medicine called Tian Yang Wan (TYW) in the treatment of HCC. The relationship of CCDC43 with immunity and cell death was analyzed by bioinformatics. Confirming the tumor suppressor effect of TYW on HCC cells by proliferation, invasion, migration and apoptosis assays. Results: First, we analyzed by proteomics that CCDC43 expression was downregulated after TYW administration and promoted the hippo pathway. Then, a large sample's transcriptome study demonstrated that elevated CCDC43 expression was strongly correlated with clinical traits and a bad prognosis in HCC patients. Next, we observed through multiple advanced algorithms that CCDC43 is involved in a variety of oncology and immunology related pathways. Notably, we found higher tumor immune microenvironment with high CCDC43 expression. Furthermore, we demonstrated that CCDC43 is associated with immune checkpoints and found that it is a sensitive indicator of a large number of chemotherapeutic agents. Subsequently, we conducted experimental investigations to demonstrate the capacity of TYW to impede proliferation and migration, while inducing apoptosis in human HCC cell lines. Finally, we performed analysis of two cell death patterns which showed CCDC43 to be strongly correlated with multiple ferroptosis factors and cuproptosis factors. Discusion: In conclusion, our study comprehensively examined the prognostic, immunological, and therapeutic implications of CCDC43 in HCC, thereby elucidating the therapeutic mechanism of action in TYW.