Changes in glucose-6-phosphate dehydrogenase expression results in altered behavior of HBV-associated liver cancer cells

Abstract

Hepatocellular carcinoma (HCC) is regarded as a major global health care issue, and chronic hepatitis B virus (HBV) infection is considered to be involved in pathogenesis of HCC. To increase knowledge of HCC pathogenesis, as well as discover potential novel molecules for anti-cancer therapy, mass spectrometry and isobaric tag for relative and absolute quantitation (iTARQ) were employed. The differences between nine HBV-related HCC and adjacent non-HCC tissue specimens were studied. In total, 222 proteins were analyzed for differential expression in the two types of samples. Among these proteins, several were further confirmed by immunohistochemical, immunoblotting, and real-time RT-PCR analysis. RNA interference induced downregulation of glucose-6-phosphate dehydrogenase (G6PD) and decreased HBV replication by fivefold by the IFN pathway. Decreased G6PD expression resulted in decreased hepatoma cell migration and invasion in cell culture. In summary, the investigation provides new information on pathogenesis of HBV infection and suggests G6PD as a novel anti-HCC target. G6PD suppression may contribute to treatment strategies for inhibiting tumor progression.

Emerging Role of the Pentose Phosphate Pathway in Hepatocellular Carcinoma

“…Using isobaric tag for relative and absolute quantitation (iTRAQ) and LC-MS/MS, in order to determine novel proteins associated with HCC, Hu et al found an increased expression of G6PD in HBV-associated HCC patients and in the HBV DNA-stably transfected cell line HepG2.2.15 (79). Moreover, the same study reported that G6PD silencing significantly inhibited HepG2 cell line invasion.…”

G6PD downregulation triggered growth inhibition and induced apoptosis by regulating STAT3 signaling pathway in esophageal squamous cell carcinoma

“…Glucose-6-phosphate dehydrogenase (G6PD), the first and key rate-limited enzyme of PPP, recently, has been verified to Xin Wang, Hongtao Liu and Xiaqing Zhang contributed equally to this work. be closely associated with tumor development and progression [9][10][11]. G6PD, an X-linked gene, consists of 13 exons and 12 introns and encodes 515 amino acids [12][13][14].…”

The association between low glucose-6-phosphate dehydrogenase activity level and hepatitis B virus infection among pre-pregnant reproductive-age Chinese females

“…Chen et al 7 investigated the role of G6PD in HBV replication and the possible mechanism of action in liver tissues and cells, and found that G6PD might be an endogenous promoting factor for HBV replication by affecting the expression www.nature.com/scientificreports www.nature.com/scientificreports/ of genes related to the type I interferon pathway. Hu et al 34 put forward through research that G6PD suppression could lead to reduced concentrations of HBsAg and HBeAg in supernatant. Ding 35 also reported that HBV infected cells were significantly lower at HBsAg, HBeAg and HBV DNA quantitative level after G6PD expression inhibited.…”

“…and serological test results. Age was split into three groups (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39), and 40-49 years old), while nationality was categorized as 'Han' and 'others' . Educational level was categorized into two groups (bachelor degree or above, high school or below).…”