Cell-specific expression of artificial microRNAs targeting essential genes exhibit potent antitumor effect on hepatocellular carcinoma cells

Mao, Chenyu; Líu, Hao; Chen, Ping; Ye, Jingjia; Teng, Lisong; Jia, Zhenyu; Cao, Jiashu

doi:10.18632/oncotarget.3302

Cited by 7 publications

(8 citation statements)

References 33 publications

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Section: Eifs and Cancermentioning

confidence: 99%

“…144 In vitro study reported the significant reduction in migratory activity and invasiveness of breast cancer cells by eIF4e knockdown using an inducible RNAi approach and in mouse model had an inhibitory effect on tumor growth and metastasis, 145 and inhibition of hepatocellular carcinoma cells could be inhibited by artificial miRNA targeting eIF4E. 146 EIF4G (175.5 kDa) is a scaffold protein around which mRNA, ribosomal subunits, and the cap-binding complex assemble in order to accomplish translation. EIF4G is a component of cap-binding complex eIF4F and it enhances the association of eIF4E with the cap structure through allosteric mechanisms.…”

Section: Eif4mentioning

confidence: 99%

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Eukaryotic translation initiation factors and cancer

et al. 2017

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Recent technological advancements have shown tremendous mechanistic accomplishments in our understanding of the mechanism of messenger RNA translation in eukaryotic cells. Eukaryotic messenger RNA translation is very complex process that includes four phases (initiation, elongation, termination, and ribosome recycling) and diverse mechanisms involving protein and non-protein molecules. Translation regulation is principally achieved during initiation step of translation, which is organized by multiple eukaryotic translation initiation factors. Eukaryotic translation initiation factor proteins help in stabilizing the formation of the functional ribosome around the start codon and provide regulatory mechanisms in translation initiation. Dysregulated messenger RNA translation is a common feature of tumorigenesis. Various oncogenic and tumor suppressive genes affect/are affected by the translation machinery, making the components of the translation apparatus promising therapeutic targets for the novel anticancer drug. This review provides details on the role of eukaryotic translation initiation factors in messenger RNA translation initiation, their contribution to onset and progression of tumor, and how dysregulated eukaryotic translation initiation factors can be used as a target to treat carcinogenesis.

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Section: Eifs and Cancermentioning

confidence: 99%

Section: Eif4mentioning

confidence: 99%

Eukaryotic translation initiation factors and cancer

et al. 2017

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“…miR-15b belongs to the miR-15/16 cluster which includes miR-15a, miR-195 and miR-16-1/2 (12,13). Previous studies have found that miR-15b is upregulated in several types of cancer, suggesting its pivotal role in tumorigenesis and progression (14,15).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-15b promotes proliferation and invasion of non-small cell lung carcinoma cells by directly targeting TIMP2

et al. 2017

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MicroRNA-15b (miR-15b) plays an important role in tumor development and progression. miR-15b functions differently in various types of malignant tumors. However, the expression pattern and role of miR-15b in non-small cell lung cancer (NSCLC) have not been elucidated. In the present study, we investigated the effect of miR-15b on the occurrence and development of lung cancer and the underlying mechanism. Lung cancer cell lines A549 and LTEP-a-2 were transfected with miR-15b inhibitor or mimic, respectively. Real-time PCR revealed that the expression level of miR-15b was significantly higher in human NSCLC tissues and NSCLC cells, than that of normal tissues and cells, respectively (P<0.05). Moreover, the effect of miR-15b on A549 and LTEP-a-2 cell viability, cell cycle, migration and invasion was further evaluated. Experiments indicated that miR‑15b knockdown inhibited the viability, cell cycle, migration and invasion in A549 cells, while upregulation of miR-15b exhibited the opposite effect. Tissue inhibitor of metallopeptidases 2 (TIMP2) protein and mRNA levels were downregulated after miR-15b overexpression in A549 and LTEP-a-2 cells, respectively. The dual-luciferase reporter gene assay implied that TIMP2 is a direct target gene of miR-15b. Our results indicate that high expression of miR-15b is associated with NSCLC and suggest that miR-15b expression may be a novel biomarker for predicting clinical outcomes in NSCLC patients. The inhibition of miR-15b may even provide helpful therapeutic strategies for the treatment of NSCLC.

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“…The apoptosis rates of HepG2/SMMC7721-pcDNA3.1/PNP cells were also substantially increased. Based on these findings, the PNP/fludarabine suicide gene system is highly cytotoxic toward HCC cells, particularly HepG2 cells, which express high levels of α-fetal protein (AFP)[ 29 ], and only in the presence of low fludarabine concentrations. All those may guide the clinical treatment of HCC.…”

Section: Discussionmentioning

confidence: 99%

An ultrasonic nanobubble-mediated PNP/fludarabine suicide gene system: A new approach for the treatment of hepatocellular carcinoma

et al. 2018

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ObjectiveThe purpose of this study is to generate an ultrasonic nanobubble (NB)-mediated purine nucleoside phosphorylase (PNP)/fludarabine suicide gene system for the treatment of human hepatocellular carcinoma (HCC).MethodsNBs were prepared from a mixture the phospholipids 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphate (DPPA), perfluoropropane gas and other materials using the high shear dispersion method. NBs treated with ultrasound irradiation functioned as a gene-transfer system, and a self-constructed suicide gene expression plasmid, pcDNA3.1(+)/PNP, treated with fludarabine functioned as a therapeutic gene. This system was used to determine the cytotoxic effects of PNP/fludarabine on HepG2 cells and SMMC7721 cells.Results1. NBs with a small diameter (208–416 nm) and at a high concentration and fine homogeneity were prepared under the optimal method. 2. The pcDNA3.1(+)/PNP plasmid was efficiently transfected into HCC cells using ultrasonic NBs. 3. At 0.75μg/ml fludarabine, PNP/fludarabine showed marked cytotoxic effects toward HepG2 and SMMC7721 cells. PNP/fludarabine achieved the same effect against both SMMC7721 and HepG2 cells but at a lower concentration of fludarabine for the latter. 4. Bystander effects: a 10–20% decrease in the cell survival rate was observed when only 5–10% of transfected cells were PNP positive.ConclusionsNBs constitute a non-toxic, stable and effective gene-delivery platform. The PNP/fludarabine suicide gene system inhibited the growth of HCC cells, induced HCC cell apoptosis, and caused a notable bystander effect at a low fludarabine concentration. This study establishes an important new method for miniaturizing microbubbles and improving a new NB-mediated approach for gene therapy of HCC.

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Cell-specific expression of artificial microRNAs targeting essential genes exhibit potent antitumor effect on hepatocellular carcinoma cells

Cited by 7 publications

References 33 publications

Eukaryotic translation initiation factors and cancer

Eukaryotic translation initiation factors and cancer

MicroRNA-15b promotes proliferation and invasion of non-small cell lung carcinoma cells by directly targeting TIMP2

An ultrasonic nanobubble-mediated PNP/fludarabine suicide gene system: A new approach for the treatment of hepatocellular carcinoma

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