RNAa-mediated overexpression of WT1 induces apoptosis in HepG2 cells

Qin, Qi‐Long; Lin, Yiwei; Zheng, Xiangyi; Chen, Hong; Mao, Qinan; Yang, Kai; Huang, Shoujiang; Zhao, Zhiyuan

doi:10.1186/1477-7819-10-11

Cited by 21 publications

(14 citation statements)

References 24 publications

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“…It has been reported that WT1 modulates the expression of BCL2, p21, and cyclin D, and suppresses p53 activity, which leads to resistance to chemotherapeutic compounds (23). BCL2 modulation by WT1 has been documented in different types of cancer cells (36,37) and involves a direct interaction with the P2 region of the BCL2 promoter (38). On the other hand, it has been observed that gemcitabine enhances WT1 expression in cholangiocarcinoma and human pancreatic cancer cells, sensitizing the cells to a WT1-specific T-cellmediated antitumor immune response (39,40).…”

Section: Discussionmentioning

confidence: 99%

shRNA-WT1 Potentiates Anticancer Effects of Gemcitabine and Cisplatin Against B16F10 Lung MetastasesIn VitroandIn Vivo

Zapata‐Benavides¹,

Thompson-Armendariz²,

Arellano-Rodríguez³

et al. 2019

In Vivo

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Background/Aim: High expression level of Wilm's tumor gene (WT1) in several types of tumors appears to confer disruption of apoptosis and resistance to chemotherapeutic drugs, and correlate with poor outcome. The aim of this work was to determine if down-regulation of WT1 expression results in decreased cell proliferation and the increased action of different types of drugs, both in vitro in B16F10 cells, and in vivo in C57BL/6 mice. Materials and Methods: Inhibition of cell proliferation by short hairpin RNA against WT1 (shRNA-WT1), cisplatin, and gemcitabine in B16F10 cells in vitro was determined by the MTT assay and analysis of clonogenic survival. The apoptosis rate was determined by flow cytometry for annexin-V-fluorescein isothiocyante and propidium iodide. Results: Compared to treatment with shRNA-WT1 alone, treatment with shRNA-WT1 in combination with drugs had a synergistic inhibitory effect on B16F10 cell proliferation, particularly for the combination of cisplatin and gemcitabine at their 25% cytotoxic concentrations in vitro. Furthermore, mice treated with shRNA-WT1 in combination with cisplatin and gemcitabine were protected in the same way as those treated with the drugs alone, but were in better physical condition. Conclusion: Decreased WT1 expression induces cell death and potentiates the action of anticancer drugs by inducing synergistic effects both in vitro and in vivo, which may be an attractive strategy in lung cancer therapy.

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Section: Discussionmentioning

confidence: 99%

shRNA-WT1 Potentiates Anticancer Effects of Gemcitabine and Cisplatin Against B16F10 Lung MetastasesIn VitroandIn Vivo

Zapata‐Benavides¹,

Thompson-Armendariz²,

Arellano-Rodríguez³

et al. 2019

In Vivo

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“…Restoring the E-cadherin gene in MDA-MB-453 breast cancer cells induced apoptosis and inhibited cell proliferation ( 21 ). Activation of the p21 gene in a variety of cancer cells, including prostate, bladder, liver, pancreas and lung cancer cells, inhibited cell proliferation and clonogenicity ( 18 , 19 , 23 , 24 ). Restoration of the p21 gene enhanced apoptotic cell death and caused G0/G1 arrest in T24 and J82 bladder cancer cells ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

Reactivation of HIC-1 gene by saRNA inhibits clonogenicity and invasiveness in breast cancer cells

Zhao

Pan

et al. 2014

Oncology Letters

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Hypermethylated in cancer 1 (HIC-1) is a tumor suppressor gene, which is epigenetically silenced in breast cancer. It is known that the loss of HIC-1, caused by promoter hypermethylation, is associated with tumor aggression and poor survival in breast carcinoma. It has been shown that small activating RNA (saRNA) targeting promoter sequences may induce gene re-expression. In the current study, saRNA was used to restore HIC-1 expression, and the effects on colony formation, invasiveness and the cell cycle in breast cancer cells were explored. dsHIC1-2998, an saRNA, exhibited activating efficacy on MCF-7 and MDA-MB-231 cancer cell lines. A clonogenicity assay showed that evident colony inhibition was induced via saRNA-mediated re-expression of HIC-1 in the two cancer cell lines. Reactivation of HIC-1 significantly inhibited cell migration and invasion, resulting in G0/G1 cell cycle arrest in these cell lines. These findings suggest that HIC-1 may be a potential target in gene therapy for the treatment of breast cancer. saRNA may function as a therapeutic option for upregulating tumor suppressor genes in breast cancer.

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“…P21, E-cadherin, and VEGF were the first described RNAa-responsive genes, and the applicability of saRNA targeting each of these genes in vivo has received attention (3,7,10,11). Importantly, recent RNAa reports evaluate the promising potential of saRNA for therapeutic intervention (7,10,12,13).…”

mentioning

confidence: 99%

RNA Activation of the Vascular Endothelial Growth Factor Gene (VEGF) Promoter by Double-Stranded RNA and Hypoxia: Role of Noncoding VEGF Promoter Transcripts

Lopez

Wagner

Hofman

et al. 2016

Molecular and Cellular Biology

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f RNA activation (RNAa) is a gene regulation process in which promoter-targeted short double-stranded RNAs (dsRNAs) or microRNAs (miRs) induce target gene expression at the transcriptional level. Here, we investigate the presence of cryptic promoter transcripts within the VEGF promoter. Single-strand sense and antisense noncoding vascular endothelial growth factor (NcVEGF) promoter transcripts are identified, and their respective expression is studied in cells transfected with a VEGF promoter targeted dsRNA, namely, dsVEGF706, in hypoxic cells and in human malignant lung tissues. Interestingly, in dsVEGF706-transfected, as well as in hypoxic cells, NcVEGF expression levels increase coordinately with coding VEGF expression. Ago2 interaction with both sense and antisense NcVEGFs is increased in hypoxic cells, whereas in dsVEGF706-transfected cells, Ago2 and the antisense strand of the dsRNA interact specifically with the sense NcVEGF transcript. Furthermore, both dsVEGF706 and ectopic NcVEGF transcripts are able to activate the VEGF promoter endogenously present or in a reporter construct. Finally, using small interfering RNA targeting Ago2, we show that RNAa plays a role in the maintenance of increased VEGF and NcVEGF expression after hypoxia. Given the central role of VEGF in major human diseases, including cancer, this novel molecular mechanism is poised to reveal promising possibilities for therapeutic interventions.

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RNAa-mediated overexpression of WT1 induces apoptosis in HepG2 cells

Cited by 21 publications

References 24 publications

shRNA-WT1 Potentiates Anticancer Effects of Gemcitabine and Cisplatin Against B16F10 Lung MetastasesIn VitroandIn Vivo

shRNA-WT1 Potentiates Anticancer Effects of Gemcitabine and Cisplatin Against B16F10 Lung MetastasesIn VitroandIn Vivo

Reactivation of HIC-1 gene by saRNA inhibits clonogenicity and invasiveness in breast cancer cells

RNA Activation of the Vascular Endothelial Growth Factor Gene (VEGF) Promoter by Double-Stranded RNA and Hypoxia: Role of Noncoding VEGF Promoter Transcripts

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