Multi-target siRNA: Therapeutic Strategy for Hepatocellular Carcinoma

Li, Tiejun; Xue, Yuwen; Wang, Guilan; Gu, Tingting; Li, Yunlong; Zhu, York Yuanyuan; Chen, Li

doi:10.7150/jca.15157

Cited by 17 publications

(15 citation statements)

References 38 publications

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“…Therefore, targeting simultaneously more than one gene product which is responsible for the tumorigenesis will be an effective therapy for xenograft tumor model. Our data is consistent with that of Tiejun et al [16], who determined that multi-target siRNAs showed better silencing effects on three targets compared with single target siRNA. These data indicate that knockdown of more than one target, which are involved in tumorigenesis; same time will be more effective than the knockdown of single target.…”

Section: Discussionsupporting

confidence: 93%

Targeting Myc and Hdac8 with a Combination of SiRNAs Inhibits Tumor Growth in a Murine Neuroblastoma Xenograft Model

Prashad

2020

GJCT

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Neuroblastoma is a common tumor of the peripheral nervous system in children. Highly aggressive MYC-drivenneuroblastoma is defined by increased MYC and/or MYCN expression. HDAC8 overexpression is associated with advanced neuroblastoma. Previously, we have demonstrated that transient knockdown of both Myc and Hdac8 using siRNA significantly suppressed neuroblastoma cells proliferation compared to knockdown of either target in vitro. In this study, we further investigated whether combinational targeting Myc and Hdac8 in neuroblastoma xenograft mice model is consistent with our previous findings. Intratumoral treatment with siRNA-MYC and siRNA-HDAC8 reduced the levels of the target MYC protein by 64% and HDAC8 by 85%; in addition, we found that the average tumor growth was reduced by 80% compared to that of control tumors treated with NC-siRNA. Our results suggest the potential therapeutic effect of the combination of siRNA-MYC and siRNA-HDAC8 for neuroblastoma treatment.

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Section: Discussionsupporting

confidence: 93%

Targeting Myc and Hdac8 with a Combination of SiRNAs Inhibits Tumor Growth in a Murine Neuroblastoma Xenograft Model

Prashad

2020

GJCT

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“…As a new member of the TM4SF family, the NET-1 gene was identified to be overexpressed in certain tumors, including HCC, gastric cancer, colorectal adenocarcinoma and skin squamous cell carcinoma ( 21 , 48 ). The present study used siRNA to inhibit NET-1 gene expression in a SMMC-7721 xenograft model; each group was treated four times.…”

Section: Discussionmentioning

confidence: 99%

“…It has been demonstrated that the NET-1 gene is involved in the division, proliferation and carcinogenesis of HCC cells ( 17 – 19 ). The level of NET-1 expression exhibits a significant association with HCC pathological grading and clinical stages ( 20 , 21 ). Therefore, the present study selected the NET-1 gene sequence as a rational target for HCC therapy ( 22 , 23 ).…”

Section: Introductionmentioning

confidence: 99%

VTIQ evaluates antitumor effects of NET‑1 siRNA by UTMD in HCC xenograft models

Liang

Shang

et al. 2018

Oncol Lett

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The present study used a virtual touch tissue imaging and quantification (VTIQ) method to investigate the change in elasticity in xenograft tumor tissue models following silencing of the neuroepithelial-transforming protein 1 (NET-1) gene by ultrasound-targeted microbubble destruction (UTMD). A total of 24 xenograft models were established by subcutaneous injection of human hepatocellular carcinoma SMMC-7721 cells in BALB/c female nude mice. Then, NET-1 small interfering RNA (siRNA)-conjugated nanobubbles and a glypican-3 antibody were synthesized. The mean and maximum shear wave speed (SWSmean and SWSmax) in the tumor tissue were measured prior to, during, and following therapy using VTIQ. The growth of the tumor size and survival time were recorded. The levels of NET-1 protein were evaluated by immunohistochemical staining. In addition, tumor, liver and kidney tissues of the nude mice were collected to confirm whether gene transfection treatment was toxic in vivo. In the UTMD delivery gene group, SWSmean was correlated with the maximum diameter of the tumor (r=0.9806, P=0.0194). The immunohistochemical staining data indicated that the level of NET-1 protein in the treated groups was significantly decreased compared with those in the control groups. Additionally, no structural damage was observed in the nude mice liver and kidney tissues following treatment. Therefore, VTIQ measurement identified potential changes in the elastic properties of the tumors, which in turn may be associated with the stages of tumor development. The delivery method, UTMD, improves the antitumor effects of NET-1 siRNA and supports gene transfection as a promising therapeutic strategy.

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“…In the study, we designed a new dsRNA molecule with triple functions based on our previous studies 19 , 24 , named triple effective RNA (teRNA), the designed teRNA combined the functions of NET-1/VEGF dual inhibition and TLR3 activation, and teRNA composed of the specific siRNAs targeting NET-1 and VEGF and dsRNA activating TLR3. The results proved that teRNA had functions of silencing both target genes (VEGF and NET-1) and activating TLR3 effectively both in mRNA and protein level (Figure 3 ).…”

Section: Discussionmentioning

confidence: 99%

“…The siRNAs that targeting human NET-1 (NCBI reference number: NM005727.3) and VEGF (NCBI reference number: NM 001287044.1) genes were designed and screened by our previous studies 19 , 24 . A specific double-stranded RNA (dsRNA) named sliRNA (BM-06) was screened for activating TLR3 provided by Biomics Biotechnologies Co. Ltd (Biomics Biotech) (China).…”

Section: Methodsmentioning

confidence: 99%

Effects of Triple Effective RNA (teRNA) on the Inhibition of Hepatocellular Carcinoma Cells

Xue¹,

Li²,

Liu³

et al. 2017

J. Cancer

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The occurrence and development of hepatocellular carcinoma (HCC) is a complicate process involved in genetic mutation and epigenetic regulation. Successful HCC therapy needs multi-targets be involved. The aim of this study was to provide a triple effective RNA (teRNA) which composed of the specific siRNAs targeting NET-1 and VEGF and dsRNA activating TLR3, and explored its anti-HCC roles and mechanism. Real-time quantitative PCR (RT-qPCR), Western blot, immunofluorescence staining, MTT, Annexin V-FITC flow cytometry, Transwell and in-vitro Angiogenesis assay were used to measure the cell biological functions and protein expression analysis. Furthermore in in-vivo mouse model, teRNA inhibited tumor growth were detected by immunohistochemistry and TUNEL assay. Results showed that the proliferation, migration and angiogenesis of HCC cells were inhibited by teRNA effectively, the cell apoptosis also was induced, and further tumor growth was suppressed in-vivo. The gene silencing mechanism of teRNA was in an Ago2-dependent manner with no interferon response. The study suggests that NET-1, VEGF and TLR3 might be better targets for HCC treatment and combined these targets in form of a multi-target small RNA, teRNA could be a stagey for the development of anti-HCC drugs.

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Multi-target siRNA: Therapeutic Strategy for Hepatocellular Carcinoma

Cited by 17 publications

References 38 publications

Targeting Myc and Hdac8 with a Combination of SiRNAs Inhibits Tumor Growth in a Murine Neuroblastoma Xenograft Model

Targeting Myc and Hdac8 with a Combination of SiRNAs Inhibits Tumor Growth in a Murine Neuroblastoma Xenograft Model

VTIQ evaluates antitumor effects of NET‑1 siRNA by UTMD in HCC xenograft models

Effects of Triple Effective RNA (teRNA) on the Inhibition of Hepatocellular Carcinoma Cells

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