Modulation of HBV replication by microRNA-15b through targeting hepatocyte nuclear factor 1α

Dai, Xiao-Peng; Zhang, Wei; Zhang, Hongfei; Sun, Shihui; Yu, Hong; Guo, Yan; Kou, Zheng; Zhao, Guangyu; Du, Lanying; Jiang, Shibo; Zhang, Jianying; Li, Junfeng; Zhou, Yusen

doi:10.1093/nar/gku260

Cited by 74 publications

(62 citation statements)

References 53 publications

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“…miR-15b was found to be highly expressed in hepatocellular carcinoma (26) and other tumors (27), indicating its potential importance in cancers. miR-15b promotes HBV replication by targeting HNF1a, and miR-15b expression in hepatocytes is downregulated by HBV in the early stages of HBV infection (30). In this study, modulation of JEV-induced inflammatory cytokine production could be a novel function of miR-15b, suggesting that the miRNA regulates tumor cell apoptosis, as well as regulates inflammation and innate immune responses.…”

Section: Discussionmentioning

confidence: 63%

“…miR15b also was shown to play very important roles in the regulation of cell proliferation and apoptosis by targeting cell cycle proteins and Bcl-2 protein (28,29). In hepatocytes, miR-15b promotes hepatitis B virus (HBV) replication by directly targeting HNF1a, whereas HBV replication represses the expression of miR-15b (30). In addition, miR-15b is involved in the expansion and differentiation of neural progenitor cells through cooperation with TET3 (31).…”

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confidence: 99%

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MicroRNA-15b Modulates Japanese Encephalitis Virus–Mediated Inflammation via Targeting RNF125

Zhu

Nie

et al. 2015

The Journal of Immunology

100

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Japanese encephalitis virus (JEV) can target CNS and cause neuroinflammation that is characterized by profound neuronal damage and concomitant microgliosis/astrogliosis. Although microRNAs (miRNAs) have emerged as a major regulatory network with profound effects on inflammatory response, it is less clear how they regulate JEV-induced inflammation. In this study, we found that miR-15b is involved in modulating the JEV-induced inflammatory response. The data demonstrate that miR-15b is upregulated during JEV infection of glial cells and mouse brains. In vitro overexpression of miR-15b enhances the JEV-induced inflammatory response, whereas inhibition of miR-15b decreases it. Mechanistically, ring finger protein 125 (RNF125), a negative regulator of RIG-I signaling, is identified as a direct target of miR-15b in the context of JEV infection. Furthermore, inhibition of RNF125 by miR-15b results in an elevation in RIG-I levels, which, in turn, leads to a higher production of proinflammatory cytokines and type I IFN. In vivo knockdown of virus-induced miR-15b by antagomir-15b restores the expression of RNF125, reduces the production of inflammatory cytokines, attenuates glial activation and neuronal damage, decreases viral burden in the brain, and improves survival in the mouse model. Taken together, our results indicate that miR-15b modulates the inflammatory response during JEV infection by negative regulation of RNF125 expression. Therefore, miR-15b targeting may constitute an interesting and promising approach to control viral-induced neuroinflammation.

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Section: Discussionmentioning

confidence: 63%

mentioning

confidence: 99%

MicroRNA-15b Modulates Japanese Encephalitis Virus–Mediated Inflammation via Targeting RNF125

Zhu

Nie

et al. 2015

The Journal of Immunology

100

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“…This process leads to the enhancement of HBV replication and expression of HBV antigens, including HBx protein, finally leading to the down-regulated expression of miR-15b in both cell lines and mice in a long cascade of events [3]. In contrast to the above facts, some findings suggest the role of sub genotype in HCC development.…”

Section: Discussionmentioning

confidence: 95%

“…Nine genotypes of HBV have been recognized on the basis of divergence in the whole DNA genome sequence of HBV [3]. HBV Genotypes show a prominent geographical pattern in their distribution.…”

Section: Introductionmentioning

confidence: 99%

“…In one study, they showed miR-15b, an important miRNA during HBV infection and hepatocellular carcinoma development, directly binds hepatocyte nuclear factor 1 (HNF1) mRNA, a negative regulator of HBV Enhancer I, to attenuate HNF1 expression and resulting in transactivation of HBV Enhancer I. This process leads to the enhancement of HBV replication and expression of HBV antigens, including HBx protein, finally leading to the down-regulated expression of miR-15b in both cell lines and mice in a long cascade of events [3].…”

Section: Introductionmentioning

confidence: 99%

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HBV Genotyping and Phylogenetic Analysis through Multiplex PCR Using Type Specific Primer Pairs in Pakistani Population

Iqbal¹,

Raza²

2016

J Bacteriol Parasitol

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Background: Hepatitis B virus causing acute and chronic hepatocellular carcinoma relics a serious health issue affecting more than 350 million people worldwide. Geographically, nine genotypes of HBV have been identified so far. Four open reading frames named (ORF P, S, F and X) renders it to specifically targets hepatocyte cells. Additionally, reverse transcription process present in the life cycle of HBV caused four order higher mutation rates as compared to adenovirus. The structural and functional differences between HBV genotypes are the mainstay to severity, complications, treatment and possibly vaccination against the virus. Hepatitis B genotyping is important for assessing its clinical implications and geographical distribution, but the sub-genotypes have been found useful for determination of specific genomic markers related to hepatocarcinogenesis and medical therapies. In Pakistan, there is no reported data available on molecular evolutionary analysis of HBV. A study was, therefore, much needed to evaluate the spectra of dominant strains prevalent here.Objectives: This study was aimed to figure out the prevalence of HBV genotypes among population in Pakistan. In this research, we focused to find out the new strains and sub genotypes of HBV. Pakistan is one of the HBV endemic countries but there is no data on subgenotypes and their recombination or the phylogenetic relatedness of the virus endemic in the country. The present study was carried out in this perspective. This study will help future researcher to study some other aspects of HBV related strains in Pakistan and also about its medical therapies. , for further analysis. All the samples were genotyped by type specific nested PCR primer pair method for 8 HBV genotypes from A through H. The patients were randomly selected irrespective of their age and gender and a written consent (parental consent in case of less than 18 years of age) was obtained. The study was approved by ethical review committee. In our research, we have used the type specific primer technique to find out the dominant strain in Pakistani populations and furthermore its phylogenetic analysis with reference sequences retrieved from NCBI databases. Results:Our results showed a direct relationship between viral load and identified genotypes and pinpointed that genotype D is the most pre-dominant genotype and prevailing in high proportions among all genotypes in Pakistani population. Mix HBV genotype infections of genotype A with B & C, D with B and C constitute about 17 percent of all the samples. Subgenotypes of different HBV strains have been identified on the basis of differences in the complete nucleotide sequences. Positive PCR results were repeated twice for confirmation. Furthermore, phylogenetic analysis revealed a homology between our reported sequences and reference sequences. The phylogenetic method showed that genotypes/sub-genotypes varies in the geographical areas and correlate strongly with ethnicity. Conclusion:Genotype D was identified and come out to be the...

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MicroRNAs: Small molecules with big impacts in liver injury

Halim

Rudayni

Chaudhary

et al. 2022

Journal Cellular Physiology

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A type of small noncoding RNAs known as microRNAs (miRNAs) fine-tune gene expression posttranscriptionally by binding to certain messenger RNA targets.Numerous physiological processes in the liver, such as differentiation, proliferation, and apoptosis, are regulated by miRNAs. Additionally, there is growing evidence that miRNAs contribute to liver pathology. Extracellular vesicles like exosomes, which contain secreted miRNAs, may facilitate paracrine and endocrine communication between various tissues by changing the gene expression and function of distal cells.The use of stable miRNAs as noninvasive biomarkers was made possible by the discovery of these molecules in body fluids. Circulating miRNAs reflect the conditions of the liver that are abnormal and may serve as new biomarkers for the early detection, prognosis, and evaluation of liver pathological states. miRNAs are appealing therapeutic targets for a range of liver disease states because altered miRNA expression is associated with deregulation of the liver's metabolism, liver damage, liver fibrosis, and tumor formation. This review provides a comprehensive review and update on miRNAs biogenesis pathways and mechanisms of miRNAmediated gene silencing. It also outlines how miRNAs affect hepatic cell proliferation, death, and regeneration as well as hepatic detoxification. Additionally, it highlights the diverse functions that miRNAs play in the onset and progression of various liver diseases, including nonalcoholic fatty liver disease, alcoholic liver disease, fibrosis, hepatitis C virus infection, and hepatocellular carcinoma. Further, it summarizes the diverse liver-specific miRNAs, illustrating the potential merits and possible caveats of their utilization as noninvasive biomarkers and appealing therapeutic targets for liver illnesses.

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Modulation of HBV replication by microRNA-15b through targeting hepatocyte nuclear factor 1α

Cited by 74 publications

References 53 publications

MicroRNA-15b Modulates Japanese Encephalitis Virus–Mediated Inflammation via Targeting RNF125

MicroRNA-15b Modulates Japanese Encephalitis Virus–Mediated Inflammation via Targeting RNF125

HBV Genotyping and Phylogenetic Analysis through Multiplex PCR Using Type Specific Primer Pairs in Pakistani Population

MicroRNAs: Small molecules with big impacts in liver injury

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