关键词: DDX27 EMT LPP alternative splicing gastric cancer metastasis

来  源:   DOI:10.3389/fgene.2022.836199   PDF(Pubmed)

Abstract:
DEAD-box helicase 27 (DDX27) was previously identified as an important mediator during carcinogenesis, while its role in gastric cancer (GC) is not yet fully elucidated. Here, we aimed to investigate the mechanism and clinical significance of DDX27 in GC. Public datasets were analyzed to determine DDX27 expression profiling. The qRT-PCR, Western blot, and immunohistochemistry analyses were employed to investigate the DDX27 expression in GC cell lines and clinical samples. The role of DDX27 in GC metastasis was explored in vitro and in vivo. Mass spectrometry, RNA-seq, and alternative splicing analysis were conducted to demonstrate the DDX27-mediated molecular mechanisms in GC. We discovered that DDX27 was highly expressed in GCs, and a high level of DDX27 indicated poor prognosis. An increased DDX27 expression could promote GC metastasis, while DDX27 knockdown impaired GC aggressiveness. Mechanically, the LLP expression was significantly altered after DDX27 downregulation, and further results indicated that LPP may be regulated by DDX27 via alternative splicing. In summary, our study indicated that DDX27 contributed to GC malignant progression via a prometastatic DDX27/LPP/EMT regulatory axis.
摘要:
DEAD-box解旋酶27(DDX27)先前被确定为癌变过程中的重要介质,虽然其在胃癌(GC)中的作用尚未完全阐明。这里,我们旨在探讨DDX27在GC中的作用机制和临床意义。分析公共数据集以确定DDX27表达谱。qRT-PCR,蛋白质印迹,和免疫组织化学分析用于研究GC细胞系和临床样品中的DDX27表达。在体外和体内探讨了DDX27在GC转移中的作用。质谱,RNA-seq,进行了选择性剪接分析,以证明DDX27介导的GC分子机制。我们发现DDX27在GC中高度表达,高DDX27水平提示预后不良。DDX27表达增高可促进GC转移,而DDX27敲低会损害GC侵袭性。机械上,DDX27下调后LLP表达显著改变,进一步的结果表明,LPP可能通过选择性剪接受到DDX27的调控。总之,我们的研究表明,DDX27通过前转移性DDX27/LPP/EMT调节轴促进GC恶性进展.
公众号