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. 2021 Nov 26;9(2):285-287.
doi: 10.1016/j.gendis.2021.11.001. eCollection 2022 Mar.

A complex signature network that controls the upregulation of PRMT5 in colorectal cancer

Han Wei  1 , Antja-Voy Hartley  1 , Aishat Motolani  1 , Guanglong Jiang  2 , Ahmad Safa  1 , Lakshmi Prabhu  1 , Yunlong Liu  2 , Tao Lu  1   2   3
Affiliations

A complex signature network that controls the upregulation of PRMT5 in colorectal cancer

Han Wei et al. Genes Dis. .
No abstract available

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Figures

Fig. 1
Figure 1
(A) qPCR was used to determine relative PRMT5 mRNA transcript levels in normal (FHC) colon cells compared to CRC cell lines (HT29, HCT116 and DLD-1). (B) FHC control cells and CRC cells HT29, HCT116 and DLD-1 were treated with CHX (60 μg/ml) for indicated times. Results from three independent experiments are presented as the mean ± SD. *P ≤ 0.05 HT29, HCT116, DLD-1 vs. FHC. (C) Luciferase reporter assay for single mutations generated within predicted binding regions for SMAD3, NF-Ya and ZNF143 using the PRMT5 2k promoter sequence (denoted as P5-2K). (D) Luciferase PRMT5 reporter assay in HT29 cells with P5-2K construct and cells with knockdown of SMAD3, NF-Ya, and ZNF143. (E) Western analyses of PRMT5 protein levels in shScramble, shSMAD3, shNF-Ya, and shZNF143 HT29 cell lines. (F) Western analyses for detection of PRMT5 protein in HT29 cells treated with IGF-1 and TGF-β2 at various time points. (G) Ingenuity pathway analysis (IPA), showing gene network links among PRMT5, NF-Ya, SMAD3 and ZNF143. (H) Box–whisker plots showing transcript levels of PRMT5, TGF-β2, ZNF143, and NF-Ya across colorectal adenocarcinoma (COAD) tumors and normal based on individual cancer stages. Individual cancer stages were based on AJCC (American Joint Committee on Cancer) pathologic tumor stage information and samples were divided into stage I, stage II, stage III and stage IV group. Courtesy of UALCAN web-portal, publicly available at http://ualcan.path.uab.edu. (I) Schematic diagram depicts a complex multiple-mechanism regulation network that could lead to upregulation of PRMT5. PRMT5 proximal promoter is positively regulated by NF-Ya, ZNF143 and SMAD3. Ligand-induced (IGF-1 and TGF-β2) activation of PRMT5 mRNA transcript levels correlates with its increased protein expression through transcription factors ZNF143 and SMAD3, respectively. Moreover, copy number amplification, increased mRNA and protein stability may also account for increase the PRMT5 protein pool frequently observed in CRC cells. Statistics: Results from three independent experiments are presented as mean ± SD. *P ≤ 0.05.
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