Circadian regulator NR1D2 regulates glioblastoma cell proliferation and motility

Oncogene
Min YuFei Lu

Abstract

Nuclear receptor NR1D2 is originally characterized as the repressor of genes involved in circadian rhythm. Recently, it is documented that NR1D2 is overexpressed in various cancers. However, the pathways and biological functions that NR1D2 involved in cancers remain poorly understood. Here, we reported that NR1D2 was abundant in human glioblastoma (GBM) tissue and cell lines but not primary human astrocytes. Silencing of NR1D2 changed the morphology of GBM cells, inhibited cell proliferation and motility, whereas had no effects on apoptosis. Importantly, based on RNA-seq and ChIP assay, we identified receptor tyrosine kinase AXL as a new transcriptional target of NR1D2 in GBM cells. AXL mediated partially the regulatory effects of NR1D2 on PI3K/AKT axis and promoted proliferation, migration, and invasion of GBM cells. Besides, NR1D2 knockdown remarkably impaired the maturation of focal adhesion and assembly of F-actin, along with downregulated p-FAK, and proteins involved in actin nucleation and polymerization (p-Rac1/Cdc42, WAVE and PFN2). Moreover, NR1D2 had more targets other than AXL to regulate epithelial-to-mesenchymal transition and cell motility in GBM cells. Altogether, our findings uncover a GBM-promoting role of NR1D...Continue Reading

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Citations

Jul 8, 2020·Journal of Experimental & Clinical Cancer Research : CR·Han ShenEric Hau
Apr 3, 2020·Combinatorial Chemistry & High Throughput Screening·Ling LiuRui Chen
Mar 21, 2020·Frontiers in Oncology·Kholoud Arafa, Marwan Emara
Mar 17, 2020·Cellular Microbiology·Arturo Aguilar-RojasNancy Guillen
Jan 12, 2021·Molecular Therapy. Nucleic Acids·Long ZhangYankun Li
Nov 20, 2020·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·F WuX Zhang
Mar 12, 2021·Chronobiology International·Le-Le ZhangYu-Kai Xiang
May 12, 2021·Journal of Experimental & Clinical Cancer Research : CR·Meng CaoXiaoqin Yuan
Aug 28, 2021·Biomedicines·María I Aroca-SiendonesJosefa León

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Methods Mentioned

BETA
reverse transcription PCR
RNA-seq
ChIP
PCR
transfect
FACS
flow cytometry
immunoprecipitation
Assay
fluorescence-activated cell sorting

Software Mentioned

QCapture Pro
Image J
GSEA
GraphPad Prism

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