miRNA-548ah promotes the replication and expression of hepatitis B virus by targeting histone deacetylase 4

Xing, Tongjing; Zhu, Jiansheng; Xian, Jianchun; Li, Ali; Wang, Xuequan; Wang, Wei; Zhang, Qian

doi:10.1016/j.lfs.2018.12.057

Cited by 33 publications

(15 citation statements)

References 28 publications

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“…In our study, higher expression of Sp1 was found in the liver tissues of CHB patients, HepG2.2.15 cells and HBV‐infected HepG2‐NTCP cells and silencing of Sp1 in HepG2.2.15 cells could increase C2 expression. Moreover, previously, lower expression of HDAC4 was found in HepG2.2.15 cells compared to HepG2 cells and was found to play an important role in the replication of HBV infection 34 . Similarly, we also found that lower expression of HDAC4 was found in the liver tissues of CHB patients, HepG2.2.15 cells and HBV‐infected HepG2‐NTCP cells.…”

Section: Discussionsupporting

confidence: 80%

Suppression of complement component 2 expression by hepatitis B virus contributes to the viral persistence in chronic hepatitis B patients

Ning

Zhen

et al. 2020

Journal of Viral Hepatitis

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Previously, we identified rare missense mutations of complement component 2 (C2) to be associated with chronic hepatitis B (CHB) by exome sequencing. However, up to now, little is known about the role of C2 in CHB. In the present study, we aimed to perform preliminary exploration about the underlying role of C2 in CHB. Serum samples from 113 CHB patients and 30 healthy controls, and liver biopsy samples from 5 CHB patients and 3 healthy controls were obtained from the Third Affiliated Hospital of Sun Yat‐sen University between January 2018 and January 2020. HepG2.2.15 and HepG2‐NTCP cells infected with HBV were used to examine the influence of HBV infection on C2 expression. IFN‐treated HepG2.2.15 cells were used to assess the effect of IFN on C2 expression. C2‐overexpressing or C2‐silencing HepG2.2.15 cells were constructed to evaluate the effect of C2 on HBV infection. Western blot and RT‐qPCR were used to measure C2 expression in biopsy samples. HBeAg and HBsAg in culture medium and C2 of serum samples were measured by ELISA. HBV‐DNA was measured by RT‐qPCR. GSE84044, GSE54747 and GSE27555 were downloaded from GEO. C2 expression in liver tissue and serum was significantly lower in CHB patients compared to healthy controls, and significantly higher C2 expression was found in CHB patients with lower ALT, AST, Scheuer grade and stages compared to CHB patients with higher ALT, AST, Scheuer grades and Scheuer stage. Besides, HBV infection could decrease C2 expression by increasing expression of Sp1 and reducing expression of HDAC4. Moreover, C2 could enhance the anti‐virus effect of IFN on HepG2.2.15 cells and also inhibit HBV replication in HepG2.2.15 cells by inhibition of p38‐MAPK signalling pathway. In conclusion, HBV may promote viral persistence in CHB patients by inhibiting C2 expression.

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Section: Discussionsupporting

confidence: 80%

Suppression of complement component 2 expression by hepatitis B virus contributes to the viral persistence in chronic hepatitis B patients

Ning

Zhen

et al. 2020

Journal of Viral Hepatitis

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“…Moreover, inhibition of HDAC4 by miRNA-548ah can inhibit the deacetylation of histones combining with cccDNA, therefore, enhancing the replication of cccDNA. 29 Additionally, acetylated histone H3 also participates in HBV DNA replication. 30 However, the exact roles of HDACi in HBV replication are still unknown.…”

Section: Discussionmentioning

confidence: 99%

Histone Deacetylase Inhibitors Romidepsin and Vorinostat Promote Hepatitis B Virus Replication by Inducing Cell Cycle Arrest

Yang

Chen

et al. 2021

Journal of Clinical and Translational Hepatology

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Background and Aims: Chronic hepatitis B virus (HBV) infection is a global public health challenge. HBV reactivation usually occurs in cancer patients after receiving cytotoxic chemotherapy or immunosuppressive therapies. Romidepsin (FK228) and vorinostat (SAHA) are histone deacetylase inhibitors (HDACi) approved by the Food and Drug Administration as novel antitumor agents. The aim of this study was to explore the effects and mechanisms of HDACi treatment on HBV replication. Methods: To assess these effects, human hepatoma cell lines were cultured and cell viability after FK228 or SAHA treatment was measured by the CCK-8 cell counting kit-8 assay. Then, HBV DNA and RNA were quantified by real-time PCR and Southern blotting. Furthermore, analysis by western blotting, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and flow cytometry was performed. Results: FK228/SAHA treatment significantly promoted HBV replication and biosynthesis in both HBV-replicating cells and HBV-transgenic mouse model. Flow cytometry assay indicated that FK228/SAHA enhanced HBV replication by inducing cell cycle arrest through modulating the expression of cell cycle regulatory proteins. In addition, simultaneous inhibition of HDAC1/2 by FK228 promoted HBV replication more effectively than the broad spectrum HDAC inhibitor SAHA. Conclusions: Overall, our results demonstrate that cell cycle blockage plays an important role in FK228/SAHAenhanced HBV replication, thus providing a potential avenue for rational use of HDACi in patients with chronic hepatitis B.

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“…While many target genes of miRNAs are known, even less information exists as to how miRNAs cooperate with histone acetylation and DNA methylation in the context of host-pathogen interaction. There is limited evidence suggesting that negative correlation between the expression of miRNAs and HDACs or HATs has been associated with infection by human pathogens 37 . Interestingly, our analysis of miRNA targets revealed that both novel and conserved miRNAs can target genes encoding methyltransferases, HATs and HDACs, which are key regulators of DNA methylation and histone modifications.…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs regulate innate immunity against uropathogenic and commensal-like Escherichia coli infections in the surrogate insect model Galleria mellonella

Mukherjee

Amsel

Kalsy

et al. 2020

Sci Rep

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Uropathogenic Escherichia coli (UPEC) strains cause symptomatic urinary tract infections in humans whereas commensal-like E. coli strains in the urinary bladder cause long-term asymptomatic bacteriuria (ABU). We previously reported that UPEC and ABU strains differentially regulate key DNA methylation and histone acetylation components in the surrogate insect host Galleria mellonella to epigenetically modulate innate immunity-related gene expression, which in turn controls bacterial growth. In this follow-up study, we infected G. mellonella larvae with UPEC strain CFT073 or ABU strain 83972 to identify differences in the expression of microRNAs (miRNAs), a class of non-coding RNAs that regulate gene expression at the post-transcriptional level. Our small RNA sequencing analysis showed that UPEC and ABU infections caused significant changes in the abundance of miRNAs in the larvae, and highlighted the differential expression of 147 conserved miRNAs and 95 novel miRNA candidates. We annotated the G. mellonella genome sequence to investigate the miRNA-regulated expression of genes encoding antimicrobial peptides, signaling proteins, and enzymatic regulators of DNA methylation and histone acetylation in infected larvae. Our results indicate that miRNAs play a role in the epigenetic reprograming of innate immunity in G. mellonella larvae to distinguish between pathogenic and commensal strains of E. coli. Urinary tract infections (UTIs) are a global public health problem, with 50% of all women experiencing a symptomatic UTI episode at least once in their lifetime. This results in 11 million medical visits and 100,000 hospital admissions in the United States every year 1,2. Uropathogenic Escherichia coli (UPEC) strains cause 70-90% of all UTIs in humans, and antibiotics are the front-line treatment option despite growing resistance among the target strains. UPEC strains infect the urinary bladder through the urethra (cystitis), and if they remain untreated, the infection can spread to the kidneys (pyelonephritis) leading to renal failure and sepsis. Unlike UPEC strains, commensal-like E. coli strains can colonize the urinary bladder in large numbers without symptoms. Such asymptomatic bacteriuria (ABU) strains have evolved from UPEC strains by losing the ability to express functional virulence factors 3-6. The ABU E. coli strain 83972 achieves long-term growth in the urinary bladder by adopting a commensal-like lifestyle. It blocks disease-associated signaling pathways and prevents symptomatic UTIs caused by more virulent UPEC strains 7-9. Innate immunity-related gene expression distinguishes between infections caused by ABU and UPEC strains in the urinary bladder. Bacterial molecular recognition patterns frequently expressed by bacterial pathogens activate different signaling pathways involved in innate immune response. Toll-like receptor (TLR) 4-mediated signaling distinguishes pathogenic from commensal strains and controls the downstream signaling pathways thus

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miRNA-548ah promotes the replication and expression of hepatitis B virus by targeting histone deacetylase 4

Cited by 33 publications

References 28 publications

Suppression of complement component 2 expression by hepatitis B virus contributes to the viral persistence in chronic hepatitis B patients

Suppression of complement component 2 expression by hepatitis B virus contributes to the viral persistence in chronic hepatitis B patients

Histone Deacetylase Inhibitors Romidepsin and Vorinostat Promote Hepatitis B Virus Replication by Inducing Cell Cycle Arrest

MicroRNAs regulate innate immunity against uropathogenic and commensal-like Escherichia coli infections in the surrogate insect model Galleria mellonella

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