West Asia Organization for Cancer Prevention (WAOCP), APOCP's West Asia Chapter. Asian Pacific Journal of Cancer Prevention 1513-7368 15 11 2014 11 01 miR-200a Inhibits Tumor Proliferation by Targeting AP-2γ in Neuroblastoma Cells 4671 4676 29318 EN Journal Article 1970 01 01 Background: MicroRNA-200a (miR-200a) has been reported to regulate tumour progression in severaltumours but little is known about its role in neuroblastoma. Our aim was to investigate the potential role andmechanism of miR-200a in neuroblastomas. Materials and Methods: Expression levels of miR-200a in tissueswere determined using RT-PCR. The effect of miR-200a and shAP-2γ on cell viability was evaluated using MTSassays, and target protein expression was determined using Western blotting and RT-PCR. Luciferase reporterplasmids were constructed to confirm direct targeting. Results were reported as mean±S.E.M and differenceswere tested for significance using the 2-tailed Students t-test. Results: We determined that miR-200a expressionwas significantly lower in neuroblastoma tumors than the adjacent non-cancer tissue. Over-expression of miR-200are reduced cell viability in neuroblastoma cells and inhibited tumor growth in mouse xenografts. We identifiedAP-2γ as a novel target for miR-200a in neuroblastoma cells. Thus miR-200a targets the 3’UTR of AP-2γ andinhibits its mRNA and protein expression. Furthermore, our result showed that shRNA knockdown of AP-2γin neuroblastoma cells results in significant inhibit of cell proliferation and tumor growth in vitro, supportingan oncogenic role of AP-2γ in neuroblastoma. Conclusions: Our study revealed that miR-200a is a candidatetumor suppressor in neuroblastoma, through direct targeting of AP-2γ. These findings re-enforce the proposalof AP-2γ as a therapeutic target in neuroblastoma.

https://journal.waocp.org/article_29318_58a9636938b9cddef4904d3cb3886ca8.pdf