In 2012 Liu et al. reported that miR-34 is an age-related miRNA regulating age-associated events and long-term brain integrity in Drosophila. They demonstrated that modulating miR-34 and its downstream target Eip74EF showed beneficial effects on age-related diseases using a Drosophila model of SCA3trQ78. These results imply that miR-34 could be a general genetic modifier and therapeutic candidate for age-related diseases. Therefore, we examined the effect of miR-34 and Eip74EF on another age-related Drosophila disease model. Using a Drosophila model expressing mutant Drosophila VCP that causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), or multisystem proteinopathy (MSP), we demonstrated that abnormal eye phenotypes generated by Drosophila VCP R152H were rescued when expressed with Eip74EF siRNA. Contrary to our expectation, miR-34 overexpression resulted in lethality when expressed with mutant VCP. Our data indicate that the other downstream targets of miR-34 might more significantly interact with mutant VCP, causing lethality. Identifying transcriptional targets of Eip74EF might provide valuable insights into diseases caused by mutations in VCP such as ALS, FTD, and MSP.

中文翻译：

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Eip74EF是果蝇中ALS-FTD连锁突变VCP表型的主要修饰子，但不是miR-34

在2012年Liu等人。报告说，miR-34是一种与年龄相关的miRNA，可调节果蝇中与年龄相关的事件和长期的大脑完整性。他们证明，使用果蝇SCA3trQ78模型，调节miR-34及其下游靶标Eip74EF对与年龄有关的疾病表现出有益的作用。这些结果表明，miR-34可能是年龄相关疾病的通用遗传修饰剂和治疗候选物。因此，我们检查了miR-34和Eip74EF对另一种与年龄相关的果蝇疾病模型的影响。使用果蝇表达突变果蝇VCP的果蝇模型来引起肌萎缩性侧索硬化（ALS）和额颞叶痴呆（FTD）或多系统蛋白病（MSP），我们证明了当果蝇ECP74EF siRNA表达后，果蝇VCP R152H产生的异常眼表型得以挽救。与我们的预期相反，miR-34过表达当与突变VCP一起表达时会导致致死性。我们的数据表明，miR-34的其他下游靶标可能与突变VCP相互作用更明显，从而导致致死性。鉴定Eip74EF的转录靶标可能为了解由VCP突变引起的疾病（如ALS，FTD和MSP）提供有价值的见解。