HES5 promotes cell proliferation and invasion through activation of STAT3 and predicts poor survival in hepatocellular carcinoma

ObjectivesHES5 is a member of the basic helix–loop–helix (bHLH) family of transcription factors, and involved in cell differentiation and proliferation in a variety of tissues other than HCC. Therefore, we have characterized HES5 and investigated its role during hepatocarcinogenesis.MethodsWe first examined the expression of HES5 in eight paired frozen HCC and adjacent noncancerous liver tissues by Western blot. Immunohistochemistry was performed to confirm our results in 58 HCC samples and evaluated the relativity between the expression of HES5 and clinicopathological variables and estimated the prognostic significance. Moreover, Western blot examined the expression of downstream proteins by siRNA HES5. Flow cytometer assay was performed to investigate the role of HES5 in the process of HCC.ResultsWe found that HES5 was upregulated in HCC specimens. The data showed that high expression of HES5 was tightly associated with histological grade (P < 0.01) and metastasis (P < 0.01), and positively correlated with proliferation marker Ki-67 (P < 0.01). Moreover, the results show that abnormal expression of HES5 influences cell growth and cell cycle of HCC cell lines. Furthermore, HES5 knockdown resulted in the reduction of p-STAT3.ConclusionThese results suggested that suppression of the HES5 leading to inhibition of proliferation may be one of the mechanisms against HCC.