PDF(Pubmed)
Abstract：
UNASSIGNED: Pervasive transcription of the eukaryotic genome generates noncoding RNAs (ncRNAs), which regulate messenger RNA (mRNA) stability and translation. MicroRNAs (miRNAs/miRs) represent a group of well-studied ncRNAs that maintain cellular homeostasis. Thus, any aberration in miRNA expression can cause diseases, including carcinogenesis. According to microRNA microarray analyses, intronic miR-617 is significantly downregulated in oral squamous cell carcinoma (OSCC) tissues compared to normal oral tissues.
UNASSIGNED: The miR-617-mediated regulation of DDX27 is established by performing experiments on OSCC cell lines, patient samples, and xenograft nude mice model. Overexpression plasmid constructs, bisulphite sequencing PCR, bioinformatics analyses, RT-qPCR, Western blotting, dual-luciferase reporter assay, and cell-based assays are utilized to delineate the role of miR-617 in OSCC.
UNASSIGNED: The present study shows that miR-617 has an anti-proliferative role in OSCC cells and is partly downregulated in OSCC cells due to the hypermethylation of its independent promoter. Further, we demonstrate that miR-617 upregulates DDX27 gene by interacting with its promoter in a dose-dependent and sequence-specific manner, and this interaction is found to be biologically relevant in OSCC patient samples. Subsequently, we show that miR-617 regulates cell proliferation, apoptosis, and anchorage-independent growth of OSCC cells by modulating DDX27 levels. Besides, our study shows that miR-617 exerts its effects through the PI3K/AKT/MTOR pathway via regulating DDX27 levels. Furthermore, the OSCC xenograft study in nude mice shows the anti-tumorigenic potential of miR-617.
UNASSIGNED: miR-617-mediated upregulation of DDX27 is a novel mechanism in OSCC and underscores the therapeutic potential of synthetic miR-617 mimics in cancer therapeutics. To the best of our knowledge, miR-617 is the 15th example of a miRNA that upregulates the expression of a protein-coding gene by interacting with its promoter.
UNASSIGNED: The miR-617-mediated regulation of DDX27 is established by performing experiments on OSCC cell lines, patient samples, and xenograft nude mice model. Overexpression plasmid constructs, bisulphite sequencing PCR, bioinformatics analyses, RT-qPCR, Western blotting, dual-luciferase reporter assay, and cell-based assays are utilized to delineate the role of miR-617 in OSCC.
UNASSIGNED: The present study shows that miR-617 has an anti-proliferative role in OSCC cells and is partly downregulated in OSCC cells due to the hypermethylation of its independent promoter. Further, we demonstrate that miR-617 upregulates DDX27 gene by interacting with its promoter in a dose-dependent and sequence-specific manner, and this interaction is found to be biologically relevant in OSCC patient samples. Subsequently, we show that miR-617 regulates cell proliferation, apoptosis, and anchorage-independent growth of OSCC cells by modulating DDX27 levels. Besides, our study shows that miR-617 exerts its effects through the PI3K/AKT/MTOR pathway via regulating DDX27 levels. Furthermore, the OSCC xenograft study in nude mice shows the anti-tumorigenic potential of miR-617.
UNASSIGNED: miR-617-mediated upregulation of DDX27 is a novel mechanism in OSCC and underscores the therapeutic potential of synthetic miR-617 mimics in cancer therapeutics. To the best of our knowledge, miR-617 is the 15th example of a miRNA that upregulates the expression of a protein-coding gene by interacting with its promoter.
摘要：
■真核基因组的普遍转录产生非编码RNA（ncRNA），调节信使RNA（mRNA）的稳定性和翻译。MicroRNAs(miRNA/miRs)代表一组充分研究的维持细胞稳态的ncRNAs。因此，miRNA表达的任何异常都会导致疾病，包括致癌作用.根据microRNA微阵列分析,与正常口腔组织相比,内含子miR-617在口腔鳞状细胞癌(OSCC)组织中显著下调。
■通过在OSCC细胞系上进行实验，建立了miR-617介导的DDX27调控，患者样本,和异种移植裸鼠模型。过表达质粒构建体,亚硫酸氢盐测序PCR，生物信息学分析，RT-qPCR,西方印迹,双荧光素酶报告分析，和基于细胞的测定用于描述miR-617在OSCC中的作用。
■本研究表明，miR-617在OSCC细胞中具有抗增殖作用，并且由于其独立启动子的超甲基化而在OSCC细胞中部分下调。Further,我们证明miR-617通过与DDX27基因启动子以剂量依赖性和序列特异性的方式相互作用来上调DDX27基因,并且发现这种相互作用在OSCC患者样本中具有生物学相关性。随后，我们显示miR-617调节细胞增殖，凋亡，和通过调节DDX27水平的OSCC细胞的锚定非依赖性生长。此外,我们的研究表明,miR-617通过调节DDX27水平,通过PI3K/AKT/MTOR途径发挥其作用.此外，裸鼠OSCC异种移植研究显示miR-617的抗肿瘤潜能。
■miR-617介导的DDX27上调是OSCC中的一种新机制，并强调了合成miR-617模拟物在癌症治疗中的治疗潜力。据我们所知,miR-617是通过与其启动子相互作用上调蛋白质编码基因表达的miRNA的第15个实例。
■通过在OSCC细胞系上进行实验，建立了miR-617介导的DDX27调控，患者样本,和异种移植裸鼠模型。过表达质粒构建体,亚硫酸氢盐测序PCR，生物信息学分析，RT-qPCR,西方印迹,双荧光素酶报告分析，和基于细胞的测定用于描述miR-617在OSCC中的作用。
■本研究表明，miR-617在OSCC细胞中具有抗增殖作用，并且由于其独立启动子的超甲基化而在OSCC细胞中部分下调。Further,我们证明miR-617通过与DDX27基因启动子以剂量依赖性和序列特异性的方式相互作用来上调DDX27基因,并且发现这种相互作用在OSCC患者样本中具有生物学相关性。随后，我们显示miR-617调节细胞增殖，凋亡，和通过调节DDX27水平的OSCC细胞的锚定非依赖性生长。此外,我们的研究表明,miR-617通过调节DDX27水平,通过PI3K/AKT/MTOR途径发挥其作用.此外，裸鼠OSCC异种移植研究显示miR-617的抗肿瘤潜能。
■miR-617介导的DDX27上调是OSCC中的一种新机制，并强调了合成miR-617模拟物在癌症治疗中的治疗潜力。据我们所知,miR-617是通过与其启动子相互作用上调蛋白质编码基因表达的miRNA的第15个实例。
