Guizhou Zhu1, Weidong Shi2, Hui Fan2, Xiubing Zhang2, Jian Xu2, Yongmei Chen2, Zhiwei Xu1, Tao Tao3, Chun Cheng4. 1. 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. 2. Department of Medical Oncology, Nantong Second Peoples Affiliated Hospital of Nantong University, 43 Xinglong Road, Nantong 226001, Jiangsu Province, People's Republic of China. 3. 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. 4. 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.
Abstract
OBJECTIVES: 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. CONCLUSION: These results suggested that suppression of the HES5 leading to inhibition of proliferation may be one of the mechanisms against HCC.
OBJECTIVES: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. CONCLUSION: These results suggested that suppression of the HES5 leading to inhibition of proliferation may be one of the mechanisms against HCC.
Authors: Eduardo H Sánchez-Mendoza; Victor Bellver-Landete; Carmen Arce; Thorsten R Doeppner; Dirk M Hermann; María Jesús Oset-Gasque Journal: PLoS One Date: 2017-05-11 Impact factor: 3.240