TGF‐β‐activated lncRNA LINC00115 is a critical regulator of glioma stem‐like cell tumorigenicity

Long non‐coding RNA s (lnc RNA s) are critical regulators in cancer. However, the involvement of lnc RNA s in TGF ‐β‐regulated tumorigenicity is still unclear. Here, we identify TGF ‐β‐activated lnc RNA LINC 00115 as a critical regulator of glioma stem‐like cell ( GSC ) self‐renewal and tumorigenicity. LINC 00115 is upregulated by TGF ‐β, acts as a mi RNA sponge, and upregulates ZEB 1 by competitively binding of miR‐200s, thereby enhancing ZEB 1 signaling and GSC self‐renewal. LINC 00115 also promotes ZNF 596 transcription by preventing binding of miR‐200s to the 5′‐ UTR of ZNF 596 , resulting in augmented ZNF 596/ EZH 2/ STAT 3 signaling and GBM tumor growth. Inhibition of EZH 2 by genetic approaches or a small molecular inhibitor markedly suppresses LINC 00115‐driven GSC self‐renewal and tumorigenicity. Moreover, LINC 00115 is highly expressed in GBM , and LINC 00115 expression or correlated co‐expression with ZEB 1 or ZNF 596 is prognostic for clinical GBM survival. Our work defines a critical role of LINC 00115 in GSC self‐renewal and tumorigenicity, and suggests LINC 00115 as a potential target for GBM treatment.