Specific activation of 2'-5'oligoadenylate synthetase gene promoter by hepatitis C virus-core protein: A potential for developing hepatitis C virus targeting gene therapy

Wang, Ying; Mao, Shanshan; He, Qiaojun; Zi, Yuan; Wen, Ji; Feng, Daxiong

doi:10.3748/wjg.15.3178

Cited by 3 publications

(2 citation statements)

References 18 publications

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“…The HepG2 cell line was stably transfected with plasmid pcDNA3.1 (−) – HCV‐core, which contained the complete coding region of the HCV‐core protein (genotype 1b), or the control plasmid pcDNA3.1 (−) – NC, to generate HepG2‐Core or HepG2‐NC cells, respectively, which were established and confirmed with a previously described method . The culture supernatants derived from HepG2‐Core and HepG2‐NC cells were collected at 1, 2, 3, 4 and 5 days.…”

Section: Methodsmentioning

confidence: 99%

miR‐1273g‐3p modulates activation and apoptosis of hepatic stellate cells by directly targeting PTEN in HCV‐related liver fibrosis

Niu

et al. 2016

FEBS Letters

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MicroRNA (miRNA) play a pivotal role in the development of liver fibrosis. However, the functions of miRNA in hepatitis C virus (HCV)‐related liver fibrosis remain unclear. In this study, we systematically analyzed the microarray data of the serum miRNA in patients with HCV‐induced hepatic fibrosis. Among 41 dysregulated miRNA, miR‐1273g‐3p was the most significantly upregulated miRNA and correlated with the stage of liver fibrosis. Overexpression of miR‐1273g‐3p could inhibit translation of PTEN, increase the expression of α‐SMA, Col1A1, and reduce apoptosis in HSCs. Hence, we conclude that miR‐1273g‐3p might affect the activation and apoptosis of HSCs by directly targeting PTEN in HCV‐related liver fibrosis.

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Section: Methodsmentioning

confidence: 99%

miR‐1273g‐3p modulates activation and apoptosis of hepatic stellate cells by directly targeting PTEN in HCV‐related liver fibrosis

Niu

et al. 2016

FEBS Letters

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“…Moreover, the activation by the core protein is a general phenomenon, regardless of HCV genotype and strain. We also reported that the HCV core protein can specifically activate the OAS gene promoter in human hepatocytes (12). Therefore, using the OAS gene promoter that is predominantly active in HCV corepositive hepatocytes is an ideal strategy to restrict cytotoxic caspase expression.…”

Section: Introductionmentioning

confidence: 97%

Inï¿½vivo treatment of HCV core-positive HepG2 cells with the transfer of recombinant caspase-3 using a 2'-5' OAS promoter

Wang

Wiegmann³

et al. 2011

Mol Med Report

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Abstract. Hepatitis C virus (HCV) is one of the most common pathogens causing liver-related morbidity and mortality, which affect 170 million individuals worldwide. There is no vaccine available, and current therapy is only partially effective. In a previous study, we constructed a recombinant caspase-3 expression vector under the 2'-5'-oligoadenylate synthetase gene (OAS) promoter (pGL3-OAS-re-caspase-3) and demonstrated that it is an effective gene therapy for HCV core-positive liver cells in vitro. In the present study, the human hepatoma cell line HepG2 was transfected with the pcDNA3.1-HCV-core-EGFP plasmid and selected by G418. Expression of HCV core protein was confirmed by RT-PCR and immunocytochemistry. Both HepG2-expressing HCV core protein and parental HepG2 cells were inoculated subcutaneously into BALB/c mice, respectively. Tumor-bearing mice were treated with an intratumoral injection of pGL3-OAS-re-caspase-3. The mice were sacrificed after 48 h. The correlation between HCV core and caspase-3 expression in tumor tissues was analyzed by immunohistochemical staining and double-label immunofluorescence staining. The subcutaneous hepatoma in vivo mouse models stably expressing HCV core protein and co-expressing HCV core protein and pGL3-OAS-re-caspase-3 were established. Double-label immunofluorescence staining showed that the percentage of co-expression of both HCV core and caspase-3 was 76±6% in the group treated with pGL3-OAS-re-caspase-3. There was a significant increase in the number of apoptotic cells in the group treated with the pGL3-OAS-re-caspase-3 system by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and transmission electron microscopy. The results suggest that the pGL3-OAS-re-caspase-3 construct can effectively induce apoptosis in HCV core-positive hepatocytes in vivo. The results presented strongly suggest that the transfer of pGL3-OAS-re-caspase-3 is an effective and promising gene therapy strategy for HCV infection.

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Establishment of an RNAi application platform in Mycobacterium tuberculosis infection models

Jung¹

2012

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Specific activation of 2'-5'oligoadenylate synthetase gene promoter by hepatitis C virus-core protein: A potential for developing hepatitis C virus targeting gene therapy

Cited by 3 publications

References 18 publications

miR‐1273g‐3p modulates activation and apoptosis of hepatic stellate cells by directly targeting PTEN in HCV‐related liver fibrosis

miR‐1273g‐3p modulates activation and apoptosis of hepatic stellate cells by directly targeting PTEN in HCV‐related liver fibrosis

Inï¿½vivo treatment of HCV core-positive HepG2 cells with the transfer of recombinant caspase-3 using a 2'-5' OAS promoter

Establishment of an RNAi application platform in Mycobacterium tuberculosis infection models

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