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Trans-splicing repair of mutant p53 suppresses the growth of hepatocellular carcinoma cells in vitro and in vivo.

ABSTRACT: Reactivation of wild-type p53 (wt-p53) function is an attractive therapeutic approach to p53-defective cancers. An ideal p53-based gene therapy should restore wt-p53 production and reduces mutant p53 transcripts simultaneously. In this study, we described an alternative strategy named as trans-splicing that repaired mutant p53 transcripts in hepatocellular carcinoma (HCC) cells. The plasmids which encoded a pre-trans-splicing molecule (PTM) targeting intron 6 of p53 were constructed and then transfected into HCC cells carrying p53 mutation. Phenotypic changes of HCC cells induced by p53-PTM were analyzed through cell cycle, cell apoptosis and the expression of p53 downstream target genes. Spliceosome mediated RNA trans-splicing (SMaRT) reduced mutant p53 transcripts and produced functional wt-p53 protein after the delivery of p53-PTM plasmids, which resulted in phenotype correction of HCC cells. In tumor xenografts established by p53-mutated HCC cells, adenovirus encoding p53-PTM induced cell cycle arrest and apoptosis and then blocked the growth of tumors in mice. Collectively, our results demonstrated for the first time that mutant p53 transcripts were functionally corrected in p53-defective HCC cells and xenografts using trans-splicing, which indicated the feasibility of using trans-splicing to repair p53 mutation in p53-defective cancers.

SUBMITTER: He X

PROVIDER: S-EPMC4346796 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Functional repair of p53 mutation in colorectal cancer cells using trans-splicing.

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5'RNA Trans-Splicing Repair of COL7A1 Mutant Transcripts in Epidermolysis Bullosa.

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Metformin Suppresses Hepatocellular Carcinoma through Regulating Alternative Splicing of LGR4.

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Galectin-9 suppresses growth of hepatocellular carcinoma in vivo

Project description:Galectin-9 suppresses growth of Li-7 cells, a cell line of human hepatocellular carcinoma, in xenograft model analysis. Micro RNA expression in xenografts of Li-7 cells, a cell line of hepatocellular carcinoma, with or without administration of galectin-9 were assessed.

2015-03-01 | E-GEOD-55666 | biostudies-arrayexpress

Galectin-9 suppresses growth of hepatocellular carcinoma in vitro

Project description:Galectin-9 suppresses growth of Li-7 cells, a cell line of human hepatocellular carcinoma, in vitro study. Micro RNA expression of Li-7 cells, a cell line of hepatocellular carcinoma, with or without administration of galectin-9 were assessed in vitro.

2015-03-01 | E-GEOD-55665 | biostudies-arrayexpress

Potential diagnostic and prognostic marker dimethylglycine dehydrogenase (DMGDH) suppresses hepatocellular carcinoma metastasis in vitro and in vivo.

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Abrus agglutinin suppresses human hepatocellular carcinoma in vitro and in vivo by inducing caspase-mediated cell death.

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Co-targeting p53-R249S and CDK4 synergistically suppresses survival of hepatocellular carcinoma cells.

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| S-EPMC7012101 | biostudies-literature

Galectin-9 suppresses growth of hepatocellular carcinoma in vitro

Project description:Galectin-9 suppresses growth of Li-7 cells, a cell line of human hepatocellular carcinoma, in vitro study.

2015-03-01 | GSE55665 | GEO

Long Noncoding RNA (lncRNA) MT1JP Suppresses Hepatocellular Carcinoma (HCC) in vitro.

Project description:Introduction:The purpose of this study was to evaluate the effects and mechanisms of the long noncoding RNA (lncRNA) MT1JP on hepatocellular carcinoma (HCC) in vitro. Patients and Methods:Thirty pairs of tumor and adjacent normal tissues were collected from HCC patients. Tissue pathology and MT1JP expression were evaluated by hematoxylin and eosin staining and in situ hybridization (ISH), respectively. The correlation between MT1JP and HCC prognosis was investigated. MTT assays, cloning, flow cytometry, transwell assays, and wound-healing assays were used to evaluate the effects of MT1JP on HCC cell lines. RT-qPCR and Western blot were used to measure the relative mRNA and protein expression levels. Results:The expression of MT1JP was downregulated in HCC tumor tissues compared with that in adjacent normal tissues, while the percent survival was significantly greater in the high MT1JP expression group than in the low MT1JP expression group (P=0.0238). In vitro, overexpression of MT1JP suppressed the proliferation, invasion, and migration, reduced colony cell number, increased cell apoptosis, and induced G1-phase cell cycle arrest in Bel-7402 and Huh-7 cells. Meanwhile, the mRNA and protein expression levels of RUNX3 and P21 were significantly upregulated, whereas those of MMP2 and MMP9 were significantly downregulated, in Bel-7402 and Huh-7 cells overexpressing MT1JP (all P<0.001). Conclusion:LncRNA MT1JP may function as a tumor suppressor in HCC. Overexpression of MT1JP suppressed HCC cell biological activities through the regulation of RUNX3.

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