The MYEOV-MYC association promotes oncogenic miR-17/93-5p expression in pancreatic ductal adenocarcinoma.
The MYEOV-MYC association promotes oncogenic miR-17/93-5p expression in pancreatic ductal adenocarcinoma.
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DOI：
10.1038/s41419-021-04387-z
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发表时间：
2021-12-20
影响因子：
9
通讯作者：
Zhu J
中科院分区：
文献类型：
--
作者：
Shen H;Ye F;Xu D;Fang L;Zhang X;Zhu J
胰腺导管腺癌是世界范围内致死率极高的恶性肿瘤。由于转移和恶性进展是PDAC临床结局不佳的主要原因，因此确定参与这些过程的关键基因和PDAC的潜在分子机制至关重要。在这项研究中，通过分析TCGA PDAC数据和匹配的GTEx数据，我们发现MYEOV表达与PDAC患者的生存率低相关，并且在癌组织中的表达高于健康组织。MYEOV水平升高导致体外和体内细胞增殖、侵袭和迁移增强。转录组分析结果显示，MYEOV介导PDAC细胞中基因表达谱的整体改变。MiRNA-seq分析显示，MYEOV调节miR-17- 5 p和miR-93- 5 p的表达水平，并且其消耗导致细胞增殖、侵袭和迁移减少，如在MYEOV敲低的PDAC细胞中观察到的。这些效应可能是由于MYEOV调节转录因子MYC在两种miRNA的基因启动子区富集的能力。此外，我们在细胞核中鉴定了含有MYEOV和MYC的复合物，为MYEOV与MYC的关联提供了额外的证据。综上所述，我们的结果表明MYEOV通过与MYC相关促进致癌miR-17/93- 5 p表达，从而促进PDAC进展。
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy worldwide. As metastasis and malignant progression are primarily responsible for the poor clinical outcomes of PDAC, identifying key genes involved in these processes and the underlying molecular mechanisms of PDAC is vital. In this study, by analyzing TCGA PDAC data and matched GTEx data, we found that MYEOV expression is associated with poor survival in PDAC patients and higher in carcinoma tissues than in healthy tissues. Elevated levels of MYEOV led to enhanced cell proliferation, invasion and migration in vitro and in vivo. Transcriptome analysis results revealed that MYEOV mediates global alterations in gene expression profiles in PDAC cells. MiRNA-seq analysis showed that MYEOV regulates the expression levels of miR-17-5p and miR-93-5p, and its depletion resulted in reduced cell proliferation, invasion and migration, as observed in MYEOV-knockdown PDAC cells. These effects are likely due to the ability of MYEOV to regulate enrichment of the transcription factor MYC at the gene promoter regions of the two miRNAs. Furthermore, we identified a complex containing MYEOV and MYC in the nucleus, providing additional evidence for the association of MYEOV with MYC. Taken together, our results suggest that MYEOV promotes oncogenic miR-17/93-5p expression by associating with MYC, contributing to PDAC progression.
肝特异性 microRNA-122 通过调节 PRKRA 促进新合成 miRNA 的积累
影响因子：
14.9
作者：
Li S;Zhu J;Fu H;Wan J;Hu Z;Liu S;Li J;Tie Y;Xing R;Zhu J;Sun Z;Zheng X
通讯作者：
Zheng X