Ben Wang1,2,3, Tian Lan4,5, Han Xiao1,2,3, Zhong-Huo Chen1,2,3, Chao Wei1,2,3, Lei-Feng Chen2, Jia-Fu Guan1,3, Rong-Fa Yuan1,3, Xin Yu1,3, Zhi-Gang Hu1,3, Hua-Jun Wu1,3, Zhi Dai6, Kai Wang7,8. 1. Hepato-Biliary-Pancreatic Surgery Division, Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China. 2. Jiangxi Province Key Laboratory of Molecular Medicine, Nanchang, 330006, China. 3. Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, 330006, China. 4. Department of Health Care Management and Medical Education, The School of Military Preventive Medicine, Fourth Military Medical University, Xi'an, 710032, China. 5. Department of Health Care Management, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China. 6. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China. 7. Hepato-Biliary-Pancreatic Surgery Division, Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China. ndefy07021@ncu.edu.cn. 8. Jiangxi Province Engineering Research Center of Hepatobiliary Disease, Nanchang, 330006, China. ndefy07021@ncu.edu.cn.
Abstract
BACKGROUND: The HSP70 family of heat shock protein plays a critical role in protein synthesis and transport to maintain protein homeostasis. Several studies have indicated that HSP70s are related to the development and occurrence of various cancers. METHODS: The relationship between the overall survival rate of hepatocellular carcinoma patients and the expression of 14 HSP70s from multiple databases, such as TCGA, ONCOMINE, cBioPortal was investigated. Western Blot and PCR were used to evaluate HSPA4 and HSPA14 expressions in various HCC cells to identify suitable cell lines for further experiments .Wound-healing assays, Transwell assays and EdU assays were used to verify the effects of HSPA4 and HSPA14 on the function of hepatocellular carcinoma cells, and statistical analysis was performed. RESULTS: Hepatocellular carcinoma tissues significantly expressed the 14 HSP70s compared to the normal samples. Besides, the high HSPA1A, HSPA1B, HSPA4, HSPA5, HSPA8, HSPA13, and HSPA14 expressions were inversely associated with the overall survival rate of patients, tumor grade, and cancer stage. A PPI regulatory network was constructed using the 14 HSP70s proteins with HSPA5 and HSPA8 at the network center. Univariate and multivariate analyses showed that HSPA4 and HSPA14 could be independent risk factors for the prognosis of hepatocellular carcinoma patients. Cell experiments have also confirmed that reducing HSPA4 and HSPA14 expressions can inhibit the invasion, metastasis, and proliferation of hepatocellular carcinoma cells. CONCLUSIONS: Therefore, the HSP70s significantly influence the occurrence and development of hepatocellular carcinoma. For instance, HSPA4 and HSPA14 can be novel therapeutic targets and prognostic biomarkers for hepatocellular carcinoma.
BACKGROUND: The HSP70 family of heat shock protein plays a critical role in protein synthesis and transport to maintain protein homeostasis. Several studies have indicated that HSP70s are related to the development and occurrence of various cancers. METHODS: The relationship between the overall survival rate of hepatocellular carcinomapatients and the expression of 14 HSP70s from multiple databases, such as TCGA, ONCOMINE, cBioPortal was investigated. Western Blot and PCR were used to evaluate HSPA4 and HSPA14 expressions in various HCC cells to identify suitable cell lines for further experiments .Wound-healing assays, Transwell assays and EdU assays were used to verify the effects of HSPA4 and HSPA14 on the function of hepatocellular carcinoma cells, and statistical analysis was performed. RESULTS:Hepatocellular carcinoma tissues significantly expressed the 14 HSP70s compared to the normal samples. Besides, the high HSPA1A, HSPA1B, HSPA4, HSPA5, HSPA8, HSPA13, and HSPA14 expressions were inversely associated with the overall survival rate of patients, tumor grade, and cancer stage. A PPI regulatory network was constructed using the 14 HSP70s proteins with HSPA5 and HSPA8 at the network center. Univariate and multivariate analyses showed that HSPA4 and HSPA14 could be independent risk factors for the prognosis of hepatocellular carcinomapatients. Cell experiments have also confirmed that reducing HSPA4 and HSPA14 expressions can inhibit the invasion, metastasis, and proliferation of hepatocellular carcinoma cells. CONCLUSIONS: Therefore, the HSP70s significantly influence the occurrence and development of hepatocellular carcinoma. For instance, HSPA4 and HSPA14 can be novel therapeutic targets and prognostic biomarkers for hepatocellular carcinoma.