Targeting excessive MYCN expression using MLN8237 and JQ1 impairs the growth of hepatoblastoma cells.

Targeting excessive MYCN expression using MLN8237 and JQ1 impairs the growth of hepatoblastoma cells. Int J Oncol. 2019 Mar 05;: Authors: Eberherr C, Beck A, Vokuhl C, Becker K, Häberle B, Von Schweinitz D, Kappler R Abstract Hepatoblastoma (HB) is the most common liver tumor in children under the age of 3 years worldwide. While many patients achieve good outcomes with surgical resection and conventional chemotherapy, there is still a high‑risk population that exhibits a poor treatment response and unfavorable prognosis, which warrants the search for novel treatment options. In recent years, it has become clear that genetic events alone are not sufficient to explain the aggressive phenotype of this embryonal malignancy. Instead, epigenetic modifications and aberrant gene expression seem to be key drivers of HB. In the present study, expression analyses such as reverse transcription‑quantitative polymerase chain reaction revealed that the oncogene, MYCN proto‑oncogene basic‑helix‑loop‑helix transcription factor (MYCN) was upregulated in HB and other pediatric liver tumors, due to the transcriptional activity of its antisense transcript MYCN opposite strand (MYCNOS). Pyrosequencing demonstrated the hypomethylated regions in the promoter of MYCN and MYCNOS, suggesting that an epigenetic mechanism may underlie the induction of aberrant expression. Transient MYCN knockdown in HB cells resulted in growth inhibition over time....
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Tags: Int J Oncol Source Type: research