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鉴定与胰腺癌不良预后相关的上调 HNRNPs。

Identification of Upregulated HNRNPs Associated with Poor Prognosis in Pancreatic Cancer.

机构信息

Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.

Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.

出版信息

Biomed Res Int. 2019 Jul 4;2019:5134050. doi: 10.1155/2019/5134050. eCollection 2019.

Abstract

Heterogeneous nuclear ribonucleoproteins (HNRNPs) are reported to play a crucial role in the pathogenic process of multiple malignancies. However, the expression patterns and prognostic values of HNRNPs in pancreatic cancer (PC) are lacking. In this study, several public databases were explored to identify the commonly upregulated HNRNPs in PC. The clinical significance of HNRNPL (heterogeneous nuclear ribonucleoproteins L) in PC was analyzed. We further performed a series of experiments to elucidate the biological functions of HNRNPL. Bioinformatics analysis including pathway enrichment and interactors with HNRNPL was used to explain the potential mechanisms of HNRNPL in PC pathogenesis. Herein, we reported that HNRNPL was commonly overexpressed in public databases and that high expression of HNRNPL in PC was positively associated with aggressive disease and poor overall survival. Downregulation of HNRNPL suppressed the abilities of migration and epithelial mesenchymal transition of PC cells in vitro, while depletion of HNRNPL did not affect the proliferation rate of PC cells. We further showed that HNRNPL might combine with RNA-binding protein, PTBP1, and function as a part of the spliceosome to regulate alternative splicing of target genes in the occurrence and development of PC. HNRNPL could be employed as an innovative prognostic biomarker and therapeutic target for PC.

摘要

异质核核糖核蛋白(HNRNPs)被报道在多种恶性肿瘤的发病机制中发挥关键作用。然而,HNRNPs 在胰腺癌(PC)中的表达模式和预后价值尚不清楚。在本研究中,我们探索了几个公共数据库,以确定 PC 中常见上调的 HNRNPs。分析了 HNRNPL(异质核核糖核蛋白 L)在 PC 中的临床意义。我们进一步进行了一系列实验来阐明 HNRNPL 在 PC 中的生物学功能。生物信息学分析包括通路富集和与 HNRNPL 相互作用的分析,用于解释 HNRNPL 在 PC 发病机制中的潜在机制。在此,我们报告 HNRNPL 在公共数据库中普遍过表达,并且 HNRNPL 在 PC 中的高表达与侵袭性疾病和总体生存率降低呈正相关。HNRNPL 的下调抑制了 PC 细胞体外迁移和上皮间质转化的能力,而 HNRNPL 的耗竭并不影响 PC 细胞的增殖率。我们进一步表明,HNRNPL 可能与 RNA 结合蛋白 PTBP1 结合,并作为剪接体的一部分发挥作用,调节 PC 发生和发展过程中靶基因的可变剪接。HNRNPL 可以作为 PC 的一种创新性预后生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5a2/6637714/d5d509aec923/BMRI2019-5134050.001.jpg

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