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Construction of HCC-targeting artificial miRNAs using natural miRNA precursors

机译:使用天然miRNA前体构建HCC靶向人工miRNA

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摘要

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, particularly in developing countries. Despite the achievements in clinical therapeutics, the HCC mortality rate remains high. A number of artificial microRNA (amiRNA)-based HCC gene therapy studies have demonstrated significant inhibition of invasion and induction of apoptosis of HCC cancer cells, indicating that this type of therapy may be a promising alternative to current therapeutics. Since the. structure of the amiRNA precursor in the specific intracellular environment is critical for the processing to mature amiRNA, a precursor structure that may be efficiently processed is desired. In this study, we constructed amiRNAs targeting firefly luciferase with the precursor structures of six HCC-abundant microRNAs: miR-18a, miR-21, miR-192, miR-221, miR-222 and miR-224, and evaluated the processing efficiency of these amiRNAs in the HCC cell lines Hep3B and HepG2 usirig a luciferase reporter system. The results demonstrated that these amiRNA precursors are capable of being expressed in HCC cells, with the miR-221 precursor-based amiRNA exhibiting the most efficient inhibition on firefly luciferase at the levels of mRNA and protein activity. This finding provides a basis for constructing HCC-targeting amiRNAs with potent processing efficiency using the precursor structure of miR-221.
机译:肝细胞癌(HCC)是全球最常见的恶性肿瘤之一,特别是在发展中国家。尽管临床治疗剂的成就,但HCC死亡率仍然很高。基于HCC基因治疗研究的许多人为MicroRNA(AmiRNA)的HCC基因治疗研究表明了对HCC癌细胞凋亡的侵袭和诱导的显着抑制,表明这种类型的治疗可能是当前治疗剂的有希望的替代品。自从。特定细胞内环境中的AmiRNA前体的结构对于成熟amiRNA的处理至关重要,期望可以有效地处理的前体结构。在这项研究中,我们构建了靶向萤火虫荧光素酶的Amirnas,其前体结构具有六个HCC丰的微大研磨方法:miR-18a,miR-21,miR-192,miR-221,miR-222和miR-224,并评估了加工效率在HCC细胞系HEP3B和HepG2 Usirig中的这些Amirnas的荧光素酶报告系统。结果表明,这些AmiRNA前体能够在HCC细胞中表达,MiR-221前体基氨基表现出在mRNA和蛋白质活性水平的萤火虫荧光素酶上的最有效抑制。该发现提供了使用MiR-221的前体结构构建具有有效加工效率的HCC靶向AMIRNA的基础。

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