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


METHODS
We 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.


RESULTS
We 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.


CONCLUSIONS
These results suggested that suppression of the HES5 leading to inhibition of proliferation may be one of the mechanisms against HCC.
Department of Medical College, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China.
Guizhou
G
Zhu
Department of Medical Oncology, Nantong Second Peoples Affiliated Hospital of Nantong University, 43 Xinglong Road, Nantong 226001, Jiangsu Province, People's Republic of China.
Weidong
W
Shi
Department of Medical Oncology, Nantong Second Peoples Affiliated Hospital of Nantong University, 43 Xinglong Road, Nantong 226001, Jiangsu Province, People's Republic of China.
Hui
H
Fan
Department of Medical Oncology, Nantong Second Peoples Affiliated Hospital of Nantong University, 43 Xinglong Road, Nantong 226001, Jiangsu Province, People's Republic of China.
Xiubing
X
Zhang
Department of Medical Oncology, Nantong Second Peoples Affiliated Hospital of Nantong University, 43 Xinglong Road, Nantong 226001, Jiangsu Province, People's Republic of China.
Jian
J
Xu
Department of Medical Oncology, Nantong Second Peoples Affiliated Hospital of Nantong University, 43 Xinglong Road, Nantong 226001, Jiangsu Province, People's Republic of China.
Yongmei
Y
Chen
Department of Medical College, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China.
Zhiwei
Z
Xu
Department of Medical College, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China. Electronic address: taotao19840324@163.com.
Tao
T
Tao
Department of Medical College, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China. Electronic address: chengchun201309@163.com.
Chun
C
Cheng
D000328:Adult; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000401:mortality* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C077478:HES5 protein, human
HES5; Hepatocellular carcinoma; Proliferation; p-STAT3