The endogenous microRNAs (miRNAs), especially the oncogenic miRNAs (OncomiRs), have been molecular targets for cancer therapy. We generated an artificially-designed interfering long non-coding RNA (lncRNAi), which contains the sequences that can complementarily bind to multiple OncomiRs and is expressed by cancer-selectively replicating adenovirus. The adenovirus-expressed lncRNAi with high level in hepatocellular carcinoma (HCC) cells competes with OncomiR target genes to bind to and consume OncomiRs, thereby achieving the targeted anti-HCC efficacy. With the targeting replication of adenovirus in HCC cells, lncRNAi was highly expressed and resulted in decreased abilities of proliferation, migration and invasion, induced cell cycle changes and apoptosis, and markedly changed the cellular mRNA and miRNA expression profiles in HCC cells. The effective antitumor effect was also demonstrated on HCC cell line xenograft models and HCC patient-derived xenograft (PDX) tumor models in nude mice. This strategy has established a technology platform with a reliable therapeutic effect for HCC therapy.
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