Inhibition of microRNA-199a-5p reduces the replication of HCV via regulating the pro-survival pathway

Wang, Hongwei; Gao, Haili; Duan, Shimiao; Song, Xiu–Peng

doi:10.1016/j.virusres.2015.05.002

Cited by 23 publications

(24 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The hypotheses that successful HCV infection critically depends on its potential to stimulate Wnt/β-catenin signaling is further supported by observations that, in addition to direct activation, HCV infection leads to elevation of the levels of miR-155 [93] and miR-199a-5p [94], in turn triggering Wnt/β-catenin signaling. MicroRNA miR-155 acts as an oncomiR by targeting the suppressor of the suppressor of cytokine signaling 1 gene ( SOCS1 ) [95], which directly inhibits APC expression, one of the major negative regulators of Wnt/β-catenin signaling [93].…”

Section: Hcv Structural Proteins Activate Wnt/β-catenin Signalingmentioning

confidence: 99%

Action and function of Wnt/β-catenin signaling in the progression from chronic hepatitis C to hepatocellular carcinoma

et al. 2016

View full text Add to dashboard Cite

Hepatitis C virus (HCV) infection is one of the leading causes of hepatocellular carcinoma (HCC) worldwide but the mechanistic basis as to how chronic HCV infection furthers the HCC process remains only poorly understood. Accumulating evidence indicates that HCV core and nonstructural proteins provoke activation of the Wnt/β-catenin signaling pathway, and the evidence supporting a role of Wnt/β-catenin signaling in the onset and progression of HCC is compelling. Convincing molecular explanations as to how expression of viral effectors translates into increased activity of the Wnt/β-catenin signaling machinery are still largely lacking, hampering the design of rational strategies aimed at preventing HCC. Furthermore, how such increased signaling is especially associated with HCC oncogenesis in the context of HCV infection remains obscure as well. Here we review the body of contemporary biomedical knowledge on the role of the Wnt/β-catenin pathway in the progression from chronic hepatitis C to cirrhosis and HCC and explore potential hypotheses as to the mechanisms involved.

show abstract

Section: Hcv Structural Proteins Activate Wnt/β-catenin Signalingmentioning

confidence: 99%

Action and function of Wnt/β-catenin signaling in the progression from chronic hepatitis C to hepatocellular carcinoma

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Among the mixture of the four miRNAs with anti-HCV potency, the let-7 family was able to suppress HCV infection by targeting insulin-like growth factor 2 mRNA-binding protein 1, an essential host factor required for HCV replication [44]. miR199a is closely related to HCV replication [45,46], whereas miR-145 was downregulated in HCV-associated hepatocellular carcinoma [57]. miR-221 was reported by our laboratory to accentuate the anti-HCV effect of IFN by targeting the inhibitory factors of IFN pathway [47].…”

Section: Discussionmentioning

confidence: 99%

“…The results suggested that most of them can complement the viral genomes (Table 1). Moreover, among the 15 miRNAs, some have already been reported to influence HCV infection [44][45][46][47].…”

Section: Umsc-exo-specific Mirnas Showed Inhibitory Effects In Hcv Inmentioning

confidence: 99%

Exosomal MicroRNAs Derived From Umbilical Mesenchymal Stem Cells Inhibit Hepatitis C Virus Infection

Qian

Fang

et al. 2016

Stem Cells Translational Medicine

135

116

View full text Add to dashboard Cite

Hepatitis C virus (HCV) is a significant global public health problem, causing more than 350,000 deaths every year. Although the development of direct-acting antivirals has improved the sustained virological response rate in HCV patients, novel anti-HCV agents with higher efficacy as well as better tolerance and cheaper production costs are still urgently needed. Cell-based therapy, especially its unique and strong paracrine ability to transfer information to other cells via extracellular vesicles such as exosomes, has become one of the most popular therapeutic methods in recent years. In our study, exosomes secreted from umbilical mesenchymal stem cells (uMSCs), which are widely used in regenerative medicine, inhibited HCV infection in vitro, especially viral replication, with low cell toxicity. Our analysis revealed that microRNAs (miRNAs) from uMSC-derived exosomes (uMSC-Exo) had their unique expression profiles, and these functional miRNAs, mainly represented by let-7f, miR-145, miR-199a, and miR-221 released from uMSC-Exo, largely contributed to the suppression of HCV RNA replication. These four miRNAs possessed binding sites in HCV RNA as demonstrated by the target prediction algorithm. In addition, uMSC-Exo therapy showed synergistic effect when combined with U.S. Food and Drug Administration-approved interferon-a or telaprevir, enhancing their anti-HCV ability and thus improving the clinical significance of these regenerative substances for future application as optimal adjuvants of anti-HCV therapy. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1190-1203 SIGNIFICANCEThis work reported, for the first time, the identification of stem cell-derived exosomes of antiviral activity. Umbilical mesenchymal stem cell-secreted exosomes inhibited hepatitis C virus infection through transporting a mixture of microRNAs complementing the viral genomes to the host cells. This finding provides insights and prospects for physiologically secreted substances for antiviral therapy.

show abstract

“…Wang H et al [30] showed that inhibition of miR-199a-5p reduces the replication of HCV via regulating the pro-survival pathway. Sun L et al [31] showed that inhibition of miR-199a-5p reduced cell proliferation in autosomal dominant polycystic kidney disease through targeting CDKN1C.…”

Section: Discussionmentioning

confidence: 99%

Atorvastatin Protects Myocardium Against Ischemia-Reperfusion Injury Through Inhibiting miR-199a-5p

Zuo¹,

Wang²,

Hu³

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

Objective: This study aimed to evaluate the protective effects of atorvastatin against myocardial ischemia/reperfusion (I/R) injury in cardiomyocytes and its possible underlying mechanism. Method: Direct cytotoxic effect of OGD/R on cardiomyocytes with and without atorvastatin pretreatment was evaluated. Effects of atorvastatin on expression of GSK-3β and miR-199a-5p were determined using RT-PCR and Western blot. In addition, GSK-3β expression with miR-199a-5p upregulation and downregulation was detected using RT-PCR, Western blot, and immunohistochemistry. Results: Pretreatment with atorvastatin significantly improved the recovery of cells viability from OGD/R (p<0.05). In addition, the atorvastatin pretreatment significantly increased GSK-3β expression both in mRNA level and protein level and decreased miR-199a-5p expression in mRNA level (p<0.05). Upregulation and downregulation of miR-199a-5p respectively decreased and increased GSK-3β expression both in mRNA level and protein level. Conclusion: These results suggested that atorvastatin provides the cardioprotective effects against I/R injury via increasing GSK-3β through inhibition of miR-199a-5p.

show abstract

Inhibition of microRNA-199a-5p reduces the replication of HCV via regulating the pro-survival pathway

Cited by 23 publications

References 34 publications

Action and function of Wnt/β-catenin signaling in the progression from chronic hepatitis C to hepatocellular carcinoma

Action and function of Wnt/β-catenin signaling in the progression from chronic hepatitis C to hepatocellular carcinoma

Exosomal MicroRNAs Derived From Umbilical Mesenchymal Stem Cells Inhibit Hepatitis C Virus Infection

Atorvastatin Protects Myocardium Against Ischemia-Reperfusion Injury Through Inhibiting miR-199a-5p

Contact Info

Product

Resources

About