American Association for Cancer Research
00085472can180688-sup-198056_2_supp_4776969_p9fygz.docx (1.1 MB)

Supplementary Figures and Index of Supplementary Tables from Oncogenic Properties of NEAT1 in Prostate Cancer Cells Depend on the CDC5L–AGRN Transcriptional Regulation Circuit

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journal contribution
posted on 2023-03-31, 01:40 authored by Xin Li, Xianteng Wang, Wanlu Song, Hui Xu, Rongyao Huang, Yuting Wang, Wenwei Zhao, Zhengtao Xiao, Xuerui Yang

This file includes Supplementary Figures 1-7 and an index of Supplementary Tables 1-5. Supplementary Figure 1: Expression of NEAT1 isoforms and silencing efficiencies. Supplementary Figure 2: Volcano plot of gene differential expression results upon silencing of NEAT1 in PC3 cells. Supplementary Figure 3: Assessment of apoptosis in PC3 and DU145 cells upon silencing of NEAT1. Supplementary Figure 4: Analysis of cell cycle distribution with FACS. Supplementary Figure 5: Assessment of cell cycle upon silencing of NEAT1. Supplementary Figure 6: Silencing efficiencies of siRNAs. Supplementary Figure 7: Quantification of DNA damage and cell cycle upon silencing of AGRN. The Supplementary Tables are Supplementary Table 1: Differential expression data upon silencing of NEAT1 in PC3 cells, Supplementary Table 2: Results of functional enrichment analysis with differentially expressed genes upon silencing of NEAT1, Supplementary Table 3: Results of MINDy with PRAD data in TCGA, Supplementary Table 4: DNA binding regions identified by CDC5L ChIP-seq, Supplementary Table 5: Binding targets of CDC5L as identified by MACS.


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National Natural Science Foundation of China

Tsinghua University Initiative Scientific Research Program

Tsinghua–Peking Joint Center for Life Sciences

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The long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) has been shown to regulate multiple cancer-related cellular activities including cell proliferation, apoptosis, and migration. In this study, we confirm that repression of NEAT1 induces DNA damage, disturbs the cell cycle, and arrests the proliferation of prostate cancer cells. By taking advantage of the prostate cancer tumor transcriptome profiles from The Cancer Genome Atlas, our data-mining pipeline identified a series of transcription factors (TF) whose regulatory activities on target genes depended on the level of NEAT1. Among them was putative TF CDC5L, which bound directly to NEAT1. Silencing NEAT1 in prostate cancer cells repressed the transcriptional activity of CDC5L, and RNA-seq and ChIP-seq analyses further revealed a handful of potential targets of CDC5L regulated by NEAT1 expression. One target of CDC5L, ARGN, mediated the strong phenotypic consequences of NEAT1 reduction, including DNA damage, cell-cycle dysregulation, and proliferation arrest. In summary, we have established the requirement of the CDC5L–AGRN circuit for the essential oncogenic role of NEAT1 in prostate cancer cells.Significance: An integrative methodology uncovers CDC5L–AGRN signaling as critical to the tumor-promoting function of long noncoding RNA NEAT1 in prostate cancer cells. Cancer Res; 78(15); 4138–49. ©2018 AACR.