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死亡盒解旋酶27通过调控胃癌转移中脂肪瘤优先伴侣的可变剪接触发上皮-间质转化

DEAD-Box Helicase 27 Triggers Epithelial to Mesenchymal Transition by Regulating Alternative Splicing of Lipoma-Preferred Partner in Gastric Cancer Metastasis.

作者信息

Jin Yirong, Yang Suzhen, Gao Xiaoliang, Chen Di, Luo Tingting, Su Song, Shi Yanting, Yang Gang, Dong Lei, Liang Jie

机构信息

State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases, Air Force Military Medical University, Xi'an, China.

Department of Digestive Disease and Gastrointestinal Motility Research Room, Xi'an Jiaotong University, Xi'an, China.

出版信息

Front Genet. 2022 May 4;13:836199. doi: 10.3389/fgene.2022.836199. eCollection 2022.

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 and . 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 alternative splicing. In summary, our study indicated that DDX27 contributed to GC malignant progression a prometastatic DDX27/LPP/EMT regulatory axis.

摘要

死亡盒解旋酶27(DDX27)先前被确定为致癌过程中的重要介质,但其在胃癌(GC)中的作用尚未完全阐明。在此,我们旨在研究DDX27在GC中的作用机制及临床意义。分析公共数据集以确定DDX27的表达谱。采用qRT-PCR、蛋白质免疫印迹和免疫组织化学分析来研究GC细胞系和临床样本中DDX27的表达。探讨了DDX27在GC转移中的作用。进行了质谱分析、RNA测序和可变剪接分析,以证明DDX27在GC中介导的分子机制。我们发现DDX27在GC中高表达,高水平的DDX27预示着预后不良。DDX27表达增加可促进GC转移,而敲低DDX27则削弱GC的侵袭性。机制上,DDX27下调后LLP表达显著改变,进一步结果表明LPP可能受DDX27可变剪接调控。总之,我们的研究表明DDX27通过一个促转移的DDX27/LPP/EMT调控轴促进GC的恶性进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e05/9114675/e2f446f653f5/fgene-13-836199-g001.jpg

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