Spermine oxidase is upregulated and promotes tumor growth in hepatocellular carcinoma
Aim: The polyamine catabolic enzyme, spermine oxidase (SMOX) is upregulated in chronic inflammatory conditions and linked to increased reactive oxygen species and DNA damage in various forms of cancers. The present study aims to explore the expression pattern and biological function of SMOX in hepatocellular carcinoma (HCC). Methods: We used quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemistry to examine SMOX expression in four HCC cell lines and 120 HCC clinical samples, and the clinical significance of SMOX was analyzed. The biological function of SMOX on HCC cells was detected both in vitro and in vivo. Results: Results showed that SMOX was overexpressed in HCC cell lines and clinical HCC tissues. Moreover, SMOX expression levels were gradually increased in normal liver, chronic hepatitis, and HCC tissues. Increased SMOX expression was correlated with poor clinical features of HCC. Patients with positive SMOX expression in tumor tissues indicated worse overall survival (P=0.008) and shorter relapse-free survival (P=0.002). Knockdown of SMOX inhibited HCC cell proliferation, arrested cell cycle at S phase, and resulted in an increase of apoptosis. The in vivo study showed that inhibition of SMOX in HCC cells significantly repressed tumor growth in nude mice. Furthermore, we showed that SMOX might exert its function by regulating the phosphatidylinositol 3'-kinase/protein kinase B signaling pathway. Conclusion: Our data indicated that SMOX upregulation could be a critical oncogene in HCC and might serve as a valuable prognostic marker and potential therapeutic target for HCC.
|Hepatocellular carcinoma, Prognosis, SMOX, Tumor growth|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Hu, T. (Tingting), Sun, D. (Dalong), Zhang, J. (Jie), Xue, R. (Ruyi), Janssen, H.L.A, Tang, W. (Wenqing), & Dong, L. (Ling). (2018). Spermine oxidase is upregulated and promotes tumor growth in hepatocellular carcinoma. Hepatology Research. doi:10.1111/hepr.13206