Regulatory mechanism of heat shock protein 90 on autophagy-related transcription factor EB in human hepatocellular carcinoma cells / 生理学报

This study was aimed to investigate the regulatory mechanism of heat shock protein 90 (Hsp90) on transcription factor EB (TFEB) during autophagy in liver cancer cells. Human hepatocellular carcinoma cell line HepG2 was treated with Hsp90 N- and C-terminal inhibitors (STA9090 and Novobiocin), respectively. Western blot and RT-PCR were used to detect the expression levels of TFEB and autophagy-related proteins. Chromatin immunoprecipitation (ChIP) assay was used to observe the ability of Hsp90α binding to the TFEB proximal promoter region. The double-luciferase gene reporter experiment was used to determine the activity of TFEB promoter. The results showed that hypoxia induced up-regulation of TFEB protein and mRNA expression levels in the HepG2 cells. The protein expression levels of TFEB, LC3 and P62 were down-regulated significantly by either STA9090 or Novobiocin, under both normoxic and hypoxic conditions. Transfection of Hsp90α-overexpressing plasmids up-regulated TFEB protein levels in either wild-type or Hsp90α knockout HepG2 cells. Hsp90 bound to the TFEB proximal promoter region and was involved in regulating TFEB transcriptional process. Whereas both STA9090 and Novobiocin inhibited Hsp90 to bind to the TFEB proximal promoter region, and decreased the activity of TFEB promoter. These results suggest that Hsp90 promotes TFEB transcription in human hepatocellular carcinoma cells by binding to the proximal promoter region, thereby up-regulating the expression levels of autophagy-related proteins.

Analysis of Human Herpes Viruses-Activated Infection Spectra in Patients with Various Immunodeficiencies / 中国实验血液学杂志

OBJECTIVE@#To study the epidemiologic characteristics of human herpes virus (HHV) activated infection in the diseases of blood system and patients received allo-HSCT by statistically analyzing the screening results of 8 human herpes viruses (HHVs) of 4164 patients in Hebei Yanda LU Dao-Pei Hospital from 2012 to 2017.@*METHODS@#PCR was used to screen 8 HHVs.@*RESULTS@#Two thousand and fifty-two patients (49.28%) were HHV-positive among 4164 patients screened. Among these patients screened, the infection spectra of 8 human HHVs in hematological diseases as well as patients received allogeneic hematopoietic stem cell transplantation of totally 2994 patients were summarized as follows: the positive rate of EBV (29.49%) was the highest, that of HCMV (23.15%), HHV-6 was 18.77% and HHV-7 was 17.64%, while the remaining 4 HHVs all≤2.1%. The rate of co-infection of various HHVs was significantly higher than that of single infection of HHV among all these disease groups except familial hemophagocytic lymphohistiocytosis, for which single EBV infection was the most common. The differences of positive rates among these 8 human HHVs in hematological diseases as well as patients received allogeneic hematopoietic stem cell transplantation were statistically significant by Chi-square test of R*C tables (χ=54.99, P＜0.05). For each HHV, the differences of positive rates among the above-mentioned disease groups were also statistically significant except HHV-8 (P＜0.05).@*CONCLUSION@#The patients with various blood diseases have different activated infection spectra of HHVs. EBV, HCMV, HHV-6 and HHV-7 are most common in HHVs infection. Different HHVs infections correlate with different hematologion diseases.