Downregulation of TLX induces TET3 expression and inhibits glioblastoma stem cell self-renewal and tumorigenesis | Zendy

Qi Cui | Zendy; Yang Su | Zendy; Peng Ye | Zendy; E Tian | Zendy; Guoqiang Sun | Zendy; Jiehua Zhou | Zendy; Guihua Sun | Zendy; Xiaoxuan Liu | Zendy; Chao Chen | Zendy; Kiyohito Murai | Zendy; Chunnian Zhao | Zendy; Krist Azizian | Zendy; Lu Yang | Zendy; Charles Warden | Zendy; Xiwei Wu | Zendy; Massimo D’Apuzzo | Zendy; Christine E. Brown | Zendy; Behnam Badie | Zendy; Ling Peng | Zendy; Arthur D. Riggs | Zendy; John J. Rossi | Zendy; Yanhong Shi | Zendy

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Downregulation of TLX induces TET3 expression and inhibits glioblastoma stem cell self-renewal and tumorigenesis

Author(s) -

Qi Cui,

Yang Su,

Peng Ye,

E Tian,

Guoqiang Sun,

Jiehua Zhou,

Guihua Sun,

Xiaoxuan Liu,

Chao Chen,

Kiyohito Murai,

Chunnian Zhao,

Krist Azizian,

Lu Yang,

Charles Warden,

Xiwei Wu,

Massimo D’Apuzzo,

Christine E. Brown,

Behnam Badie,

Ling Peng,

Arthur D. Riggs,

John J. Rossi,

Yanhong Shi

Publication year - 2016

Publication title -

nature communications

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.559

H-Index - 365

ISSN - 2041-1723

DOI - 10.1038/ncomms10637

Subject(s) - small hairpin rna , gene knockdown , cancer research , carcinogenesis , glioblastoma , downregulation and upregulation , stem cell , biology , suppressor , cell growth , cell culture , microbiology and biotechnology , cancer , genetics , gene

Glioblastomas have been proposed to be maintained by highly tumorigenic glioblastoma stem cells (GSCs) that are resistant to current therapy. Therefore, targeting GSCs is critical for developing effective therapies for glioblastoma. In this study, we identify the regulatory cascade of the nuclear receptor TLX and the DNA hydroxylase Ten eleven translocation 3 (TET3) as a target for human GSCs. We show that knockdown of TLX expression inhibits human GSC tumorigenicity in mice. Treatment of human GSC-grafted mice with viral vector-delivered TLX shRNA or nanovector-delivered TLX siRNA inhibits tumour development and prolongs survival. Moreover, we identify TET3 as a potent tumour suppressor downstream of TLX to regulate the growth and self-renewal in GSCs. This study identifies the TLX-TET3 axis as a potential therapeutic target for glioblastoma.

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