Upregulation of cystatin SN promotes hepatocellular carcinoma progression and predicts a poor prognosis

• Published in: Journal of cellular physiology 2019-12, Vol.234 (12), p.22623-22634
• Main Authors: Cui, Yifeng, Sun, Dan, Song, Ruipeng, Zhang, Shugeng, Liu, Xirui, Wang, Yan, Meng, Fanzheng, Lan, Yaliang, Han, Jihua, Pan, Shangha, Liang, Shuhang, Zhang, Bo, Guo, Hongrui, Liu, Yufeng, Lu, Zhaoyang, Liu, Lianxin
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Biomarkers, Tumor; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Line, Tumor; Cell Movement; Cell Proliferation; cystatin SN; Cystatins; Cysteine proteinase; epithelial‐mesenchymal transition; Female; Gene Expression Regulation, Neoplastic - physiology; Hepatocellular carcinoma; Humans; Invasiveness; Liver cancer; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Mesenchyme; Metastases; Mice; Middle Aged; Multivariate analysis; Neoplasms, Experimental; Original; Original s; Phosphatidylinositol 3-Kinases; Prognosis; prognostic marker; Proteinase inhibitors; Proto-Oncogene Proteins c-akt; Salivary Cystatins - genetics; Salivary Cystatins - metabolism; Tumors; Up-Regulation; Xenografts; Xenotransplantation
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.28828

Cystatin SN, a specific cysteine protease inhibitor, is thought to be involved in various malignant tumors. Therefore, we evaluated the role of cystatin SN in hepatocellular carcinoma (HCC). Notably, cystatin SN was elevated in tumorous samples and cells. Moreover, overexpression of cystatin SN was correlated with tumor diameter and TNM stage. Cox multivariate analysis displayed that cystatin SN was an independent prognosis indicator and that high cystatin SN level was associated with a dismal prognosis. Moreover, cystatin SN enhancement facilitated the proliferation, migratory, and invasive potential of Huh7 and HCCLM3 cells, whereas cystatin SN knockdown caused the opposite effect. Cystatin SN also modulated the epithelial‐mesenchymal transition progression through the PI3K/AKT pathway. In vivo cystatin SN promoted HCCLM3 cell growth and metastasis in xenograft mice model. Thus, cystatin SN was involved in HCC progression and could be a latent target for HCC treatment. Cystatin SN was elevated in tumorous samples and cells, and overexpression of cystatin SN was correlated with tumor diameter and TNM stage. Cystatin SN enhancement facilitated the proliferation, migratory, and invasive potential of Huh7 and HCCLM3 cells, whereas cystatin SN knockdown caused the opposite effect. Thus, cystatin SN was involved in hepatocellular carcinoma (HCC) progression and could be a latent target for HCC treatment.