STUB1 promotes the degradation of HSPB1 and induces ferroptosis in lung cancer cells.

Lung cancer is a common malignancy characterized by ferroptosis, an iron-dependent form of cell death caused by excessive lipid peroxidation. The disruption of the ubiquitination system plays a crucial role in tumor development and spread. In recent years, there has been increasing interest in utilizing ferroptosis for lung cancer treatment; however, the precise mechanism of how ubiquitination modulates ferroptosis remains unclear. We used databases to analyze STUB1 expression patterns in lung cancer tissues compared to normal tissues and performed immunohistochemistry. The functional role of STUB1 was investigated through gain-of-function and loss-of-function experiments both in vitro and in vivo. Malondialdehyde levels, Fe2+ content, and cell viability assays were employed to evaluate ferroptosis status. Downstream targets of STUB1 were identified through screening and validated using immunoprecipitation and ubiquitination assays. Our findings demonstrate that STUB1 is downregulated in lung cancer cells and functions as an inhibitor of their growth and metastasis both in vitro and in vivo while promoting ferroptosis. Mechanistically, STUB1 induces ferroptosis through E3 ligase-dependent degradation of the ferroptosis suppressor HSPB1. Furthermore, our study elucidated the specific types and sites of modification on HSPB1 mediated by STUB1. This research establishes STUB1 as a tumor suppressor influencing proliferation of lung cancer cells as well as the epithelial-mesenchymal transition process associated with it. Importantly, our work highlights the role of STUB1 in ubiquitination-mediated degradation of HSPB1, providing insights for potential treatments for lung cancer.

Liver fibrosis is a major risk factor for liver regeneration: A comparison between healthy and fibrotic liver.

BACKGROUND: Blood flow factors, such as congestion or ischemia after hepatectomy, have a significant impact on liver regeneration, but with the popularization of precise hepatectomy technology, segmental hepatectomy without congestion or ischemia has become the preferred treatment. Our aim is to investigate the factors affecting liver regeneration after hepatectomy without blood flow changes, and to provide clinical evidence for surgeons on the timing of second hepatectomy for cirrhosis patients with hepatocellular carcinoma (HCC). METHODS: This study retrospectively analyzed data from patients who underwent right hepatectomy without middle hepatic vein (MHV) in West China Hospital between January 2016 and January 2018. Eighteen living-donors without MHV as normal group and 45 HCC patients, further classified into 3 subgroups based on the severity of fibrosis using the Scheure system. Demographic data, pre- and postoperative liver function indexes, and remnant liver volume (RLV) were retrospectively compared. We also analyzed the remnant liver regeneration rate (RLRR) post-operatively in each group. The significant indexes in univariate analysis were further analyzed using both receiver operating characteristic (ROC) analysis and multivariate regression analysis. RESULTS: Liver regeneration occurred in both living-donor and HCC groups after hepatectomy; the RLRRs at 1 month were 59.46 ±â€Š10.39% and 57.27 ±â€Š4.77% (P = .509), respectively. Regeneration in the cirrhosis group occurred more slowly and less completely compared with that in other groups. The regeneration rate in the first 6 months showed rapid increase and the RLRR reached above 70% in cirrhosis group. Multivariate and ROC analyses revealed that Alb and the hepatic fibrosis grade in the early postoperative period were significant predictors of remnant liver regeneration. CONCLUSION: The liver regenerated in all HCC patients; however, regeneration was significantly slower and less complete compared with the normal liver, especially in the patients with cirrhosis. Therefore, it can be concluded that the degree of liver fibrosis is a major predictor of liver regeneration. Furthermore, the optimal time for second resection in recurrent HCC patients with cirrhosis was 6 months after the first operation.