Isotope Science Center, The University of Tokyo, Tokyo 113-0032, Japan.
Cancer Genomics and Precision Medicine, Department of Medicine, Asahikawa Medical University, Asahikawa 078-8510, Japan.
Int J Mol Sci. 2022 Jan 2;23(1):496. doi: 10.3390/ijms23010496.
The RNA exosome is a multi-subunit ribonuclease complex that is evolutionally conserved and the major cellular machinery for the surveillance, processing, degradation, and turnover of diverse RNAs essential for cell viability. Here we performed integrated genomic and clinicopathological analyses of 27 RNA exosome components across 32 tumor types using The Cancer Genome Atlas PanCancer Atlas Studies' datasets. We discovered that the gene, which encodes a barrel component of the RNA exosome, was amplified across multiple cancer types. We further found that alteration is associated with a poor prognosis of pancreatic cancer patients. Moreover, we demonstrated that EXOSC4 is required for the survival of pancreatic cancer cells. EXOSC4 also repressed expression and destabilized mRNA by promoting its degradation. Furthermore, knockdown of BIK and SESN2 could partially rescue pancreatic cells from the reduction in cell viability caused by EXOSC4 knockdown. Our study provides evidence for EXOSC4-mediated regulation of and mRNA in the survival of pancreatic tumor cells.
RNA 外切体是一种进化上保守的多亚基核糖核酸酶复合物，是细胞内监视、加工、降解和周转各种 RNA 的主要机制，这些 RNA 对细胞活力至关重要。在这里，我们使用癌症基因组图谱泛癌症图谱研究的数据集，对 32 种肿瘤类型中的 27 种 RNA 外切体成分进行了综合基因组和临床病理分析。我们发现，编码 RNA 外切体桶状成分的 基因在多种癌症类型中扩增。我们进一步发现， 改变与胰腺癌患者预后不良相关。此外，我们证明 EXOSC4 是胰腺癌细胞存活所必需的。EXOSC4 还通过促进其降解来抑制 表达并使 mRNA 不稳定。此外，下调 BIK 和 SESN2 可部分挽救胰腺细胞因 EXOSC4 下调而导致的细胞活力降低。我们的研究为 EXOSC4 介导的调节 在胰腺肿瘤细胞存活中的作用提供了证据。
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