Eradication of neuroblastoma by suppressing the expression of a single long noncoding RNA
Seminar Title: Eradication of neuroblastoma by suppressing the expression of a single long noncoding RNA
Speaker: Dr Tao Liu, UNSW
Date and Time: 1:30pm to 2:30pm, Friday 30 October
Seminar Room: CB11.04.300
Seminar Chairman: Associate Professor Jinyan Li (Jinyan.email@example.com)
Neuroblastoma is the most common solid tumour in early childhood, and accounts for approximately 15% of all childhood cancer death. The majority of patient with neuroblasotma due to N-Myc gene amplification die of the disease. Our RNA-sequencing identified 5 transcripts, including RP1X, considerably differentially expressed between N-Myc gene amplified and non-amplified human neuroblastoma cell lines. Affymetrix microarray studies revealed that DEPDC was one of few genes considerably down-regulated in neuroblastoam cells after transfection with RP1X siRNAs. Depletion of RP1X or DEPDC significantly reduced N-Myc protein phosphorylation at Serine 62, N-Myc protein stabilization and neuroblastoma cell proliferation/survival. In human neuroblastoma tissues from the European Neuroblastoma Research Consortium, high levels of RP1X gene expression correlated with N-Myc target geneset activation, DEPDC gene expression and poor patient prognosis. Importantly, knocking-down RP1X gene expression in mice xenografted with human neuroblastoma cells eradicated tumours. In conclusion, this study identifies the novel long non-coding RNA RP1X as an important regulator of N-Myc protein stability and neuroblastoma tumourigenesis.
Originally trained as a medical practitioner specialising in neurology, Dr Tao Liu studied for a PhD degree at UNSW Australia on the role of inflammatory mediators in chronic pain due to nerve injury. He then worked on the role of MIC-1, a new member of the transforming growth factor beta superfamily, in cancer cell proliferation, survival/apoptosis and metastasis at St Vincent's Centre for Applied Medical Research. Tao moved to Children's Cancer Institute as a Senior Research Officer in 2003. Since 2004, he has been focusing his research on the roles of histone deacetylases, histone demethylases, histone methyltransferases and long noncoding RNAs in modulating gene transcription and tumourigenesis, and the roles of histone deacetylase inhibitors and histone methyltransferase inhibitors as anticancer agents. He was promoted to Project Leader in 2009 and Group Leader in 2011. Over the past decade, Tao has authored a number of peer-reviewed publications in high impact scientific journals including Lancet, Journal of the National Cancer Institute, Proceedings of the National Academy of Sciences USA, Nature Reviews Cancer, Nature Communications, Journal of Clinical Oncology, PLOS Genetics, Cell Death & Differentiation, and Cancer Research.