Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Baculovirus (BV) is a potential gene delivery vector but only mediates transient transgene expression and easily inactivated by human complement. To this end, we intend to develop a novel bivalent BV vector for complement resistance and sustained transgene expression, and evaluate its effect in anti-angiogenesis gene therapy. The results showed that the hybrid bivalent BV significantly prolonged the expression of enhanced green fluorescent protein (eGFP) in vitro for at least 90 days at over 109 a.u. total fluorescence intensity, and exhibited significantly higher complement resistance. The control BV-mediated eGFP expression gradually declined within 15 days and showed lower transduction efficiency. In vivo studies confirmed that the hybrid bivalent BV exhibited longer duration of eGFP expression and higher transduction efficacy than the control BVs. Based on these findings, we further constructed a hybrid BV expressing the antiangiogenic fusion protein containing human endostatin and angiostatin (hEA). The hybrid BV-expressed hEA significantly prolonged the expression level of hEA with enhanced anti-angiogenic activities compared to the control groups, as evidenced by ELISA, cell proliferation, migration and tubular formation assays. With the stable expression of hEA, the hybrid BV conferred hEA more significant inhibitory effect on hepatocellular carcinoma tumor growth and significantly extended the life span of mice. These data implicate that the SB-based BV surface display system may have broad prospects as a novel platform for gene therapy of tumors.
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PMID:Development of a novel bivalent baculovirus vectors for complement resistance and sustained transgene expression and its application in anti-angiogenesis gene therapy. 3184 43

Angiogenesis is critical for the development, progression, and metastasis of hepatocellular carcinoma (HCC), but the roles of miR-3064-5p in HCC angiogenesis are still unknown. In this study, the roles of miR-3064-5p in HCC angiogenesis were studied in 192 HCC patients, xenograft mouse models, and HCC cell lines. The results showed that miR-3064-5p expression was significantly decreased in HCC tissues and cells, and downregulated miR-3064-5p was associated with upregulated angiogenic potential of HCC. MiR-3064-5p inhibited proangiogenic VEGFA and angiogenin expressions but induced antiangiogenic endostatin and MMP12 expressions, finally leading to suppression of HCC angiogenesis, as shown by the decline in intratumoral microvessel density (MVD). Moreover, miR-3064-5p was inversely correlated with lncRNA MALAT1 and FOXA1. FOXA1 bound to and interacted with CD24 and then regulated Src phosphorylation. MiR-3064-5p played an antiangiogenic role by inhibiting the FOXA1/CD24/Src pathway, whereas oncogenic MALAT1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-3064-5p to alleviate the suppressive effect on the FOXA1 pathway. HCC patients with high miR-3064-5p, low MALAT1, or low FOXA1 expression had a better prognosis with longer overall survival and recurrence-free survival. In univariate and multivariate analyses, miR-3064-5p was identified as the independent prognostic predicator for HCC progression and patient survival. Taken together, miR-3064-5p exerts an antiangiogenic role by targeting the FOXA1/CD24/Src pathway but oncogenic lncRNA MALAT1 acts as a ceRNA to sponge miR-3064-5p. MiR-3064-5p is of great clinical significance and is a novel prognostic indicator and an attractive therapeutic target for HCC.
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PMID:MicroRNA-3064-5p sponged by MALAT1 suppresses angiogenesis in human hepatocellular carcinoma by targeting the FOXA1/CD24/Src pathway. 3191 39


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