TY - JOUR
T1 - CBIO-06THE NOVEL E2F1-REGULATED LONG NON-CODING RNA TALNEC2 IS HIGHLY EXPRESSED IN GBM FROM SHORT-TERM SURVIVORS AND REGULATES THE MIGRATION, STEMNESS AND RADIATION RESPONSE OF GLIOMA STEM CELLS
AU - Lee, Hae Kyung
AU - Brodie, Shlomit
AU - Finnis, Susan
AU - Cazacu, Simona
AU - Xiang, Cunli
AU - Xin, Hong
AU - Kalkanis, Steve
AU - Poisson, Laila
AU - Ginsburg, Doron
AU - Brodie, Chaya
PY - 2015/11/9
Y1 - 2015/11/9
N2 - Despite advances in novel therapeutic approaches for the treatment of glioblastoma (GBM), prognosis remains extremely poor and median survival of 12-14 months has not changed significantly. Therefore, there is an urgent need for the identification of molecular mechanisms that play a role in overall survival. Recent studies implicated long non-coding RNAs (lncRNAs) in gliomagenesis and patient survival. Here, we analyzed the expression and functions of a novel lncRNA, TALNEC2 that was identified by us as an E2F1-activated lncRNAs using RNA seq. The expression of the lncRNA was examined in astrocytic tumors, in GBM specimens derived from short- (< 9 months) and long- (>3 years) term survivors, and in GSCs and glioma cell lines. TALNEC2 was selectively expressed in glioma cell lines and GSCs compared with normal neural cells. Similarly, we found higher expression of this lncRNA in astrocytic tumors in a grade-dependent manner and a significant (P < 0.05) increased expression in specimens derived from short-term survivors. Silencing of TALNEC2 resulted in a decrease in cell proliferation (54.2 ± 6.1 in A172; 48.2 ± 5.5 in U87 cells), decrease in cell migration and self-renewal of GSCs (67.4 ± 11.9) and in increased sensitivity of GSCs to radiation (3Gy, P < 0.01). TALNEC2 was highly enriched in exosomes secreted from GSCs and played a role in the interaction of GSCs with their microenvironment, especially with astrocytes and microglia. Finally, we found that silencing of TALNEC2 in GSCs resulted in inhibition of xenograft growth and prolonged animal survival. Using miRNA sequencing we identified specific miRNAs that were altered in the silenced cells. In conclusion, we identified a novel E2F1-regulated lncRNA that is highly expressed in GBM from short-term survivors. The expression of TALNEC2 is associated with the increased tumorigenic potential of GSCs and with their resistance to radiation. We conclude that TALNEC2 is an attractive therapeutic target for the treatment of GBM.
AB - Despite advances in novel therapeutic approaches for the treatment of glioblastoma (GBM), prognosis remains extremely poor and median survival of 12-14 months has not changed significantly. Therefore, there is an urgent need for the identification of molecular mechanisms that play a role in overall survival. Recent studies implicated long non-coding RNAs (lncRNAs) in gliomagenesis and patient survival. Here, we analyzed the expression and functions of a novel lncRNA, TALNEC2 that was identified by us as an E2F1-activated lncRNAs using RNA seq. The expression of the lncRNA was examined in astrocytic tumors, in GBM specimens derived from short- (< 9 months) and long- (>3 years) term survivors, and in GSCs and glioma cell lines. TALNEC2 was selectively expressed in glioma cell lines and GSCs compared with normal neural cells. Similarly, we found higher expression of this lncRNA in astrocytic tumors in a grade-dependent manner and a significant (P < 0.05) increased expression in specimens derived from short-term survivors. Silencing of TALNEC2 resulted in a decrease in cell proliferation (54.2 ± 6.1 in A172; 48.2 ± 5.5 in U87 cells), decrease in cell migration and self-renewal of GSCs (67.4 ± 11.9) and in increased sensitivity of GSCs to radiation (3Gy, P < 0.01). TALNEC2 was highly enriched in exosomes secreted from GSCs and played a role in the interaction of GSCs with their microenvironment, especially with astrocytes and microglia. Finally, we found that silencing of TALNEC2 in GSCs resulted in inhibition of xenograft growth and prolonged animal survival. Using miRNA sequencing we identified specific miRNAs that were altered in the silenced cells. In conclusion, we identified a novel E2F1-regulated lncRNA that is highly expressed in GBM from short-term survivors. The expression of TALNEC2 is associated with the increased tumorigenic potential of GSCs and with their resistance to radiation. We conclude that TALNEC2 is an attractive therapeutic target for the treatment of GBM.
UR - https://www.mendeley.com/catalogue/6f458801-599d-3b0d-a2e6-3d5573eb9b2b/
U2 - 10.1093/neuonc/nov209.06
DO - 10.1093/neuonc/nov209.06
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SN - 1522-8517
VL - 17
SP - v55-V65
JO - Neuro-Oncology
JF - Neuro-Oncology
IS - Suppl 5
ER -