Objective To investigate the mechanism by which the SLC7A11 gene regulates the development and progression of hepatocellular carcinoma(HCCLM3)through the ferroptosis pathway,and to evaluate its potential as a therapeutic target.Methods Differentially expressed ferroptosis-related genes in liver cancer were screened based on data from the TCGA and ICGC databases.Detection of mRNA expression levels of TERT,MIOX,MYCN,NOX4,and SLC7A11 in tumor and adjacent non-tumorous tissues from 32 clinical liver cancer samples using qRT-PCR.Further analysis of SLC7A11 and its downstream molecules SLC3A2,GSS,and GPX4 was performed through qRT-PCR,Western blot,and IHC to assess expression levels and tissue distribution.A stable SLC7A11-knockdown HCCLM3 cell line was constructed and used to establish a subcutaneous xenograft tumor model in nude mice to evaluate its effect on tumor growth.Mice were divided into two groups(n=6 per group):HCCLM3+sh-NC and HCCLM3+sh-SLC7A11.Serum levels of IL-6,IL-1β,and TNF-α were measured using ELISA.Histopathological changes in tumor tissues were examined by H&E staining,and the expression of key genes was validated through multiple approaches.Results Bioinformatics analysis showed high expression of SLC7A11 in hepatocellular carcinoma tissues(P<0.05),significantly associated with poor patient prognosis.Clinical sample validation revealed significantly higher expression of SLC7A11,SLC3A2,GSS,and GPX4 in cancer tissues compared to control groups(All P<0.05).SLC7A11 knockdown significantly inhibited tumor volume and wet weight(P<0.05),and H&E staining showed reduced vascular density in the sh-SLC7A11 group.ELISA results showed elevated serum levels of IL-1β,IL-6,and TNF-α in the sh-SLC7A11 group.qRT-PCR,Western blot,and IHC all showed significantly downregulated expression of SLC7A11,SLC3A2,GSS,and GPX4 in tumor tissues(All P<0.05).Conclusion SLC7A11 inhibits ferroptosis by regulating the GSH-GPX4 axis,promoting hepatocellular carcinoma cell growth.Targeted inhibition of SLC7A11 can induce tumor cell ferroptosis and suppress tumor progression,suggesting it may be an important therapeutic target for hepatocellular carcinoma.

BACKGROUNDTo establish a cohort for the study of risk factors of lung cancer, and to support the study of early biomarkers and prevention of lung cancer.

METHODSDesigned a special population-based prospectively dynamic cohort among radon- and arsenic-exposed tin miners aged 40 or more years old with at least 10 years of occupational exposure in Yunnan Province, P.R.China. The mass screenings with sputum cytology and chest X-ray were conducted annually. The baseline information was collected for assessing demographic characteristics and risk factors. The multiple sputum specimens, chest radiographs and numerous biologic specimens have been collected and stored.

RESULTSFrom 1992-1999, 9143 miners have been enrolled and 460 new cases of lung cancer have been found. There had 47655 person-time chest radiographs and 46625 person-time sputum cytology among the cohort in 8 years. The relative risks of age-adjusted exposure to chronic bronchitis, silicosis, and tobacco were 1.73, 1.46, and 1.32 respectively.

CONCLUSIONSA cohort of unique occupationally-exposed tin miners with an extensive biologic specimen repository and data bank has been successfully established. Although occupational exposures are the predominant risk factors among the high risk miners, lung cancer risk is also associated with chronic obstructive lung disease (chronic bronchitis and silicosis) and a number of measures of exposure to tobacco smoke, including early age of first use, duration, and cumulative exposure.