Protein arginine methyltransferase 1 is a novel regulator of MYCN in neuroblastoma

Eberhardt, Allison; Hansen, Jeanne N.; Koster, Jan; Lotta, Louis T.; Wang, Simeng; Livingstone, Emmett; Qian, Kun; Valentijn, Linda J.; Zheng, Y. George; Schor, Nina F.; Li, Xingguo

doi:10.18632/oncotarget.11556

Cited by 22 publications

(37 citation statements)

References 18 publications

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“…In human melanoma, Li, et al reported that PRMT1 is overexpressed in human melanoma and may regulate tumour growth and metastasis via targeting ALCAM [8]. Eberhardt, et al indicated that PRMT1 is a novel regulator of MYCN, which implicates PRMT1 as a potential therapeutic target in neuroblastoma pathogenesis [28]. These reports might also support the correlation between PRMT1 and HCC progression, specifically tumour growth and metastasis, which was shown in this study.…”

Section: Discussionsupporting

confidence: 82%

PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signalling Pathway

Zhang

Jiang

Zhong

et al. 2018

Cell Physiol Biochem

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Background/Aims: Although it has been widely accepted that protein arginine methyltransferase 1 (PRMT1) is a cancer-promoting gene in various cancers, the mechanism of PRMT1 in hepatocellular carcinoma (HCC) requires more exploration. This study aimed to investigate the role of PRMT1 in HCC growth and metastasis. Methods: We compared PRMT1 expression and clinicopathological characteristics using paired HCC and adjacent noncancerous liver tissues from 210 patients and immunohistochemistry analyses. Cell proliferation, colony formation and migration were determined in HCC cell lines with PRMT1 overexpression or downregulation through MTT, crystal violet and Boyden chamber assays. Tumour growth was monitored in a xenograft model, and intrahepatic metastasis models were established. Results: PRMT1 expression was greatly increased in clinical HCC samples and strongly associated with poor prognosis and recurrence; PRMT1 expression was also positively correlated with microvascular invasion (P = 0.024), tumour differentiation (P = 0.014), tumour size (P = 0.002), and portal vein tumour thrombus (PVTT) (P = 0.028). Cell proliferation, colony formation and migration in vitro were enhanced by PRMT1 upregulation and decreased by PRMT1 downregulation in HCC cell lines. Moreover, low PRMT1 expression resulted in slow tumour growth and decreased tumour weight in vivo, as well as tumour metastasis. These phenotypes were associated with STAT3 signalling pathway activation. Cryptotanshinone, a STAT3 inhibitor, inhibited STAT3 phosphorylation and reversed the HCC phenotype of PRMT1 expression. Conclusions: We revealed a significant role for PRMT1 in HCC progression and metastasis in vitro and in vivo via STAT3 signalling pathway activation. PRMT1 may be a potential novel prognostic biomarker and new therapeutic target for HCC.

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Section: Discussionsupporting

confidence: 82%

PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signalling Pathway

Zhang

Jiang

Zhong

et al. 2018

Cell Physiol Biochem

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“…PRMT1 also regulates other transcription factors that are involved in regulation of cell‐cycle progression and proliferation, such as FOXOs, p53, c‐Myc, as well as upstream signaling molecules involved in proliferation, epidermal growth factor receptor . We analyzed PRMT1 KO mouse gene expression and used IPA analysis to find the main upstream regulators affected by PRMT1.…”

Section: Discussionmentioning

confidence: 99%

Protein arginine methyl transferase 1– and Jumonji C domain‐containing protein 6–dependent arginine methylation regulate hepatocyte nuclear factor 4 alpha expression and hepatocyte proliferation in mice

et al. 2018

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“…c-Myc is an important transcription factor in regulating myeloid cell functions (8 -10). Previous studies on c-Myc and N-Myc regulation by PRMT1 suggest that PRMT1 regulates Myc gene expression (20,21) and function (21).…”

Section: Arginine Methylation Is Required For C-myc-p300 Interactionmentioning

confidence: 93%

Arginine methylation regulates c-Myc–dependent transcription by altering promoter recruitment of the acetyltransferase p300

Tikhanovich¹,

Zhao²,

Bridges

et al. 2017

Journal of Biological Chemistry

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Protein arginine methyltransferase 1 (PRMT1) is an essential enzyme controlling about 85% of the total cellular arginine methylation in proteins. We have shown previously that PRMT1 is an important regulator of innate immune responses and that it is required for M2 macrophage differentiation. c-Myc is a transcription factor that is critical in regulating cell proliferation and also regulates the M2 transcriptional program in macrophages. Here, we sought to determine whether c-Myc in myeloid cells is regulated by PRMT1-dependent arginine methylation. We found that PRMT1 activity was necessary for c-Myc binding to the acetyltransferase p300. PRMT1 inhibition decreased p300 recruitment to c-Myc target promoters and increased histone deacetylase 1 (HDAC1) recruitment, thereby decreasing transcription at these sites. Moreover, PRMT1 inhibition blocked c-Myc-mediated induction of several of its target genes, including peroxisome proliferator-activated receptor γ () and mannose receptor C-type 1 (), suggesting that PRMT1 is necessary for c-Myc function in M2 macrophage differentiation. Of note, in primary human blood monocytes, p300-c-Myc binding was strongly correlated with PRMT1 expression, and in liver sections, PRMT1, c-Myc, and M2 macrophage levels were strongly correlated with each other. Both PRMT1 levels and M2 macrophage numbers were significantly lower in livers from individuals with a history of spontaneous bacterial peritonitis, known to have defective cellular immunity. In conclusion, our findings demonstrate that PRMT1 is an important regulator of c-Myc function in myeloid cells. PRMT1 loss in individuals with cirrhosis may contribute to their immune defects.

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Protein arginine methyltransferase 1 is a novel regulator of MYCN in neuroblastoma

Cited by 22 publications

References 18 publications

PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signalling Pathway

PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signalling Pathway

Protein arginine methyl transferase 1– and Jumonji C domain‐containing protein 6–dependent arginine methylation regulate hepatocyte nuclear factor 4 alpha expression and hepatocyte proliferation in mice

Arginine methylation regulates c-Myc–dependent transcription by altering promoter recruitment of the acetyltransferase p300

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