Limits...
Protein arginine methyltransferase 5 is a key regulator of the MYCN oncoprotein in neuroblastoma cells.

Park JH, Szemes M, Vieira GC, Melegh Z, Malik S, Heesom KJ, Von Wallwitz-Freitas L, Greenhough A, Brown KW, Zheng YG, Catchpoole D, Deery MJ, Malik K - Mol Oncol (2014)

Bottom Line: Immunoblotting of NB cell-lines shows that high PRMT5 expression is strongly associated with MYCN-amplification (P < 0.004, Mann-Whitney U-test) and immunohistochemical analysis of primary NBs reveals that whilst PRMT5 protein is ubiquitously expressed in the cytoplasm of most cells, MYCN-amplified tumours exhibit pronounced nuclear PRMT5 staining.PRMT5 knockdown in MYCN-overexpressing cells, including the SHEP-21N cell-line with inducible MYCN expression leads to a dramatic decrease in MYCN protein and MYCN-associated cell-death in SHEP-21N cells.Together our studies implicate PRMT5 in a novel mode of MYCN post-translational regulation and suggest PRMT5 plays a major role in NB tumorigenesis.

View Article: PubMed Central - PubMed

Affiliation: Cancer Epigenetics Laboratory University of Bristol, Bristol BS8 1TD, UK.

Show MeSH

Related in: MedlinePlus

(A) High PRMT5 mRNA expression correlates with MYCN amplification (MYCN-amp) in NB. Data analysed is from Valentijn et al., 2012, using the R2 microarray analysis and visualization platform (http://r2.amc.nl). Tumours with no MYCN amplification (MYCN-un) show lower PRMT5 mRNA expression. Kaplan Meier curve showing high PRMT5 mRNA expression correlates with poor prognosis. The Bonferroni corrected probability (Bonf P) is shown. (B) Kaplan Meier curve showing high PRMT5 mRNA expression correlates with poor prognosis in MYCN-unamplified tumours.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4359099&req=5

undfig3: (A) High PRMT5 mRNA expression correlates with MYCN amplification (MYCN-amp) in NB. Data analysed is from Valentijn et al., 2012, using the R2 microarray analysis and visualization platform (http://r2.amc.nl). Tumours with no MYCN amplification (MYCN-un) show lower PRMT5 mRNA expression. Kaplan Meier curve showing high PRMT5 mRNA expression correlates with poor prognosis. The Bonferroni corrected probability (Bonf P) is shown. (B) Kaplan Meier curve showing high PRMT5 mRNA expression correlates with poor prognosis in MYCN-unamplified tumours.


Protein arginine methyltransferase 5 is a key regulator of the MYCN oncoprotein in neuroblastoma cells.

Park JH, Szemes M, Vieira GC, Melegh Z, Malik S, Heesom KJ, Von Wallwitz-Freitas L, Greenhough A, Brown KW, Zheng YG, Catchpoole D, Deery MJ, Malik K - Mol Oncol (2014)

(A) High PRMT5 mRNA expression correlates with MYCN amplification (MYCN-amp) in NB. Data analysed is from Valentijn et al., 2012, using the R2 microarray analysis and visualization platform (http://r2.amc.nl). Tumours with no MYCN amplification (MYCN-un) show lower PRMT5 mRNA expression. Kaplan Meier curve showing high PRMT5 mRNA expression correlates with poor prognosis. The Bonferroni corrected probability (Bonf P) is shown. (B) Kaplan Meier curve showing high PRMT5 mRNA expression correlates with poor prognosis in MYCN-unamplified tumours.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4359099&req=5

undfig3: (A) High PRMT5 mRNA expression correlates with MYCN amplification (MYCN-amp) in NB. Data analysed is from Valentijn et al., 2012, using the R2 microarray analysis and visualization platform (http://r2.amc.nl). Tumours with no MYCN amplification (MYCN-un) show lower PRMT5 mRNA expression. Kaplan Meier curve showing high PRMT5 mRNA expression correlates with poor prognosis. The Bonferroni corrected probability (Bonf P) is shown. (B) Kaplan Meier curve showing high PRMT5 mRNA expression correlates with poor prognosis in MYCN-unamplified tumours.
Bottom Line: Immunoblotting of NB cell-lines shows that high PRMT5 expression is strongly associated with MYCN-amplification (P < 0.004, Mann-Whitney U-test) and immunohistochemical analysis of primary NBs reveals that whilst PRMT5 protein is ubiquitously expressed in the cytoplasm of most cells, MYCN-amplified tumours exhibit pronounced nuclear PRMT5 staining.PRMT5 knockdown in MYCN-overexpressing cells, including the SHEP-21N cell-line with inducible MYCN expression leads to a dramatic decrease in MYCN protein and MYCN-associated cell-death in SHEP-21N cells.Together our studies implicate PRMT5 in a novel mode of MYCN post-translational regulation and suggest PRMT5 plays a major role in NB tumorigenesis.

View Article: PubMed Central - PubMed

Affiliation: Cancer Epigenetics Laboratory University of Bristol, Bristol BS8 1TD, UK.

Show MeSH
Related in: MedlinePlus