Circular RNA Profiling Reveals That circRNA_104433 Regulates Cell Growth by Targeting miR-497-5p in Gastric Cancer
CANCER MANAGEMENT AND RESEARCH
Authors: Wei, Weiyuan; Mo, Xianwei; Yan, Linhai; Huang, Mingwei; Yang, Yang; Jin, Qinwen; Zhong, Huage; Cao, Wenlong; Wu, Kun; Wu, Liucheng; Li, Zhao; Wang, Tingan; Qin, Yuzhou; Chen, Jiansi
Abstract
Background: The role and mechanism of hsa_circRNA_104433 in gastric cancer (GC) are further elucidated. Materials and methods: CircRNA_104433 was selected by circRNA microarrays and GEO database. qRT-PCR was used to analyze the expression of circRNA_104433 in GC. The role of circRNA_104433 in GC cells was evaluated based on cell cycle progression, cell proliferation, cell apoptosis, and tumor xenograft experiment assay. To explore the mechanisms of circRNA_104433 in GC TCGA database, STRING version, qRT-PCR and luciferase assay were performed. Furthermore, the prognostic value of CDC25A in GC was determined based on the GEO database. Results: The level of circRNA_104433 showed upregulation in GC tissues, and the expression of it showed a positive correlation with the degree of differentiation and the size of the tumor. Knockdown of circRNA_104433 inhibited cell cycle transition, and cell proliferation, while promoted cell apoptosis in GC. CircRNA_104433 directly binds to miR-497-5p, which directly regulates CDC25A. The median survival period of GC patients with high expression levels of CDC25A was 21.3 months, which was shorter than those with low group expression of CDC25A (35.9 months). The cell cycle proteins CDK1, CDK2, CCNB1, PKMYT1, CDC20, CHEK1 and CDC25A were coexpressed with CDC25A. Conclusion: These findings suggested that knockdown of circRNA_104433 expression suppressed tumor development in GC.
Antagonistic activities of CDC14B and CDK1 on USP9X regulate WT1-dependent mitotic transcription and survival
NATURE COMMUNICATIONS
Authors: Dietachmayr, Michael; Rathakrishnan, Abirami; Karpiuk, Oleksandra; von Zweydorf, Felix; Engleitner, Thomas; Fernandez-Saiz, Vanesa; Schenk, Petra; Ueffing, Marius; Rad, Roland; Eilers, Martin; Gloeckner, Christian Johannes; von Hohenberg, Katharina Clemm; Bassermann, Florian
Abstract
Regulation of mitosis secures cellular integrity and its failure critically contributes to the development, maintenance, and treatment resistance of cancer. In yeast, the dual phosphatase Cdc14 controls mitotic progression by antagonizing Cdk1-mediated protein phosphorylation. By contrast, specific mitotic functions of the mammalian Cdc14 orthologue CDC14B have remained largely elusive. Here, we find that CDC14B antagonizes CDK1-mediated activating mitotic phosphorylation of the deubiquitinase USP9X at serine residue 2563, which we show to be essential for USP9X to mediate mitotic survival. Starting from an unbiased proteome-wide screening approach, we specify Wilms' tumor protein 1 (WT1) as the relevant substrate that becomes deubiquitylated and stabilized by serine 2563-phosphorylated USP9X in mitosis. We further demonstrate that WT1 functions as a mitotic transcription factor and specify CXCL8/IL-8 as a target gene of WT1 that conveys mitotic survival. Together, we describe a ubiquitin-dependent signaling pathway that directs a mitosis-specific transcription program to regulate mitotic survival.
COA
Publication 
Loading ......
