**6. Conclusions**

In conclusion, the upregulation of sCLU expression at early staging of HCC is considered to promote tumor development, which may be related to the phosphorylation of AKT/GSK-3β. An increasing number of reports have provided evidence that sCLU level could be a novel biomarker for HCC diagnosis and prognosis, and there will be of great significance for the individualized treatment in HCC patients. The sCLU regulating signaling pathways could be critical to unraveling the solution for MDR in HCC. Therefore, silencing sCLU gene transcription and inhibiting sCLU expression by specific Custirsen inhibition have provided a new mechanism insight into molecular-targeted therapy for HCC in injected- or orthotopic model, indicated that sCLU gene would be a potential molecular-targeted for HCC therapy. Further study found that sCLU contributed to HCC migration and EMT *in vitro*, and metastasis *in vivo*. Although additional preclinical and clinical trials are necessary to explore the sCLU role in HCC, targeting the oncogenic sCLU could validate the approach as a systemic therapy to increase chemotherapy sensitivity.
