Title: 
Targeting TUG1, a Notch-regulated Non-coding RNA, as Potential Therapeutics for Human Gliomas.

 

Yutaka Kondo 
Department of Epigenomics, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan, E-mail: ykondo@med.nagoya-cu.ac.jp

 

Abstract:
Tumorigenic process involves developmental program, which is analogous to cellular reprogramming. During this process, epigenetic mechanisms play roles as effectors and modulators of reprogramming and establish functions in tumorigenesis. Cancer cells have plasticity in response to extracellular signals, being capable to functionally adapt to their microenvironment. The Notch signaling pathway is essential for glioma stem cell (GSC) maintenance through incompletely understood mechanisms. We found that TUG1, a long non-coding RNA (lncRNA), is induced by Notch signaling and is highly expressed in GSCs. TUG1 in the nucleus physically interacted with polycomb repressive complex 2 and promoted locus-specific methylation of histone H3K27, which resulted in dynamic suppression of neuronal differentiation-associated genes. Further, cytoplasmic TUG1 increased the expression of stemness-associated genes through quenching of endogenous microRNA. Inhibition of TUG1 induces GSC differentiation and efficiently represses GSC growth both in vitro and in vivo. Our data indicate that the Notch-regulated lncRNA, TUG1, plays pivotal roles in maintaining the self-renewal properties of GSC. Targeting the GSC population and its associated underlying mechanism may be a novel strategy in glioblastoma treatment. In this talk, I would provide an overview of the epigenetic alterations in human cancers and discusses novel therapeutic strategies targeting epigenetic alterations.

 

References:
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