Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
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Query: UNIPROT:P10415 (
Bcl-2
)
33,771
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Simultaneous silencing of multiple up-regulated genes is an attractive and viable strategy to treat many incurable diseases including cancer. Herein we used dual gene targeted siRNA (DGT siRNA) conjugate composed of
NET-1
and VEGF siRNA sequences in the same backbone could inhibit growth and angiogenesis HCC. DGT siRNA showed a further down regulation on VEGF mRNA and protein levels compared with
NET-1
siRNA or VEGF siRNA, but not on
NET-1
expression. It also exhibited greater suppression on proliferation and trigger of apoptosis in HepG2 cells than
NET-1
siRNA or VEGF siRNA; this could be explained by the significant down regulation of cyclin D1 and
Bcl-2
. A lower level of ANG2 mRNA and protein was detected in HUVEC cultured with supernatant of HepG2 cells treated with DGT siRNA than that of VEGF siRNA or
NET-1
siRNA, resulting in much more inhibited angiogenesis of HUVEC. Tumor growth was inhibited and microvessel density dropped in the xenograft tumor models compared to the untreated controls.
NET-1
and VEGF silencing play a key role in inhibiting hepatocellular cell proliferation, promoting apoptosis, and reducing angiogenesis. Simultaneous silencing of
NET-1
and VEGF using DGT siRNA construct may provide an advantageous alternative in development of therapeutics for Hepatocellular carcinoma.
...
PMID:Inhibition of hepatocellular carcinoma growth and angiogenesis by dual silencing of NET-1 and VEGF. 2363 6
The simultaneous silencing of multiple upregulated genes is an attractive and viable strategy to treat many incurable diseases including cancer. In the present study, skin squamous cell carcinoma (SSCC) tissue microarray was constructed and the expression of
NET-1
and survivin was identified. The high expression of
NET-1
and survivin gene in SSCC was confirmed as an important event for the formation and development of the cancer. A total of 100 primary SSCC patients were included in the present study. Expression of
NET-1
and survivin in cancer cells was evaluated immunohistochemically in tissue microarrays. The interaction between
NET-1
and survivin in SSCC by co-immunoprecipitation was subsequently verified by producing the siRNA sequence targeting the single gene (siRNA-
NET-1
and siRNA-survivin) as well as
NET-1
and survivin gene (one-chain-double-target siRNA). The levels of
NET-1
and survivin mRNA and protein expression in A431 cells were detected by RT-qPCR and western blotting, and the expression of related genes including vascular endothelial growth factor (VEGF), cortactin,
Bcl-2
, caspase-3 and -8 was identified using RT-qPCR. The protein localization and expression of
NET-1
and survivin in A431 cells were documented by immunohistochemistry and immuno-fluorescence staining. The proliferation and apoptosis of A431 cells were detected by CCK-8 assay and flow cytometry (FCM). The tissue microarray showed that
NET-1
and survivin were highly expressed in SSCC, while the correlation analysis showed
NET-1
expression was positively associated with survivin. In addition, we reported that using the one-chain-double-target siRNA conjugate composed of
NET-1
and survivin siRNA sequences in the same backbone inhibited proliferation and promoted apoptosis of SSCC. The one-chain-double-target siRNA showed further downregulation on
NET-1
and survivin mRNA and protein levels compared with
NET-1
siRNA or survivin siRNA. It also exhibited greater suppression on proliferation and triggering of apoptosis in A431 cells than
NET-1
siRNA or survivin siRNA. This result may be explained by the significant downregulation of VEGF, cortactin and
Bcl-2
, and upregulation of caspase-3 and -8.
NET-1
and survivin were overexpressed in SSCC and an interaction between
NET-1
and survivin was identified. The one-chain-double-target siRNA appears to be superior in inhibiting cell proliferation and promoting apoptosis compared with the single target siRNA.
NET-1
and survivin may have correlative signaling pathways with VEGF, cortactin,
Bcl-2
, caspase-3 and -8. Simultaneous silencing of
NET-1
and survivin using one-chain-double-target siRNA thus provides an advantageous alternative in the development of therapeutics for SSCC.
...
PMID:Inhibition of skin squamous cell carcinoma proliferation and promote apoptosis by dual silencing of NET-1 and survivin. 2608 Aug 53
