TY - JOUR
T1 - RBM5-AS1 is critical for self-renewal of colon cancer stem-like cells
AU - Cecilia, Serena Di
AU - Zhang, Fan
AU - Sancho, Ana
AU - Li, Side
AU - Aguilo, Francesca
AU - Sun, Yifei
AU - Rengasamy, Madhumitha
AU - Zhang, Weijia
AU - Vecchio, Luigi Del
AU - Salvatore, Francesco
AU - Walsh, Martin J.
N1 - Publisher Copyright:
© 2016 AACR.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Cancer-initiating cells (CIC) undergo asymmetric growth patterns that increase phenotypic diversity and drive selection for chemotherapeutic resistance and tumor relapse. WNT signaling is a hallmark of colon CIC, often caused by APC mutations, which enable activation of b-catenin and MYC. Accumulating evidence indicates that long noncoding RNAs (lncRNA) contribute to the stem-like character of colon cancer cells. In this study, we report enrichment of the lncRNA RBM5-AS1/LUST during sphere formation of colon CIC. Its silencing impaired WNT signaling, whereas its overexpression enforced WNT signaling, cell growth, and survival in serum-free media. RBM5-AS1 has been little characterized previously, and we determined it to be a nuclearretained transcript that selectively interacted with b-catenin. Mechanistic investigations showed that silencing or overexpression of RBM5-AS1 caused a respective loss or retention of b-catenin from TCF4 complexes bound to the WNT target genes SGK1, YAP1, and MYC. Our work suggests that RBM5-AS1 activity is critical for the functional enablement of colon cancer stem-like cells. Furthermore, it defines the mechanism of action of RBM5- AS1 in the WNT pathway via physical interactions with b-catenin, helping organize transcriptional complexes that sustain colon CIC function.
AB - Cancer-initiating cells (CIC) undergo asymmetric growth patterns that increase phenotypic diversity and drive selection for chemotherapeutic resistance and tumor relapse. WNT signaling is a hallmark of colon CIC, often caused by APC mutations, which enable activation of b-catenin and MYC. Accumulating evidence indicates that long noncoding RNAs (lncRNA) contribute to the stem-like character of colon cancer cells. In this study, we report enrichment of the lncRNA RBM5-AS1/LUST during sphere formation of colon CIC. Its silencing impaired WNT signaling, whereas its overexpression enforced WNT signaling, cell growth, and survival in serum-free media. RBM5-AS1 has been little characterized previously, and we determined it to be a nuclearretained transcript that selectively interacted with b-catenin. Mechanistic investigations showed that silencing or overexpression of RBM5-AS1 caused a respective loss or retention of b-catenin from TCF4 complexes bound to the WNT target genes SGK1, YAP1, and MYC. Our work suggests that RBM5-AS1 activity is critical for the functional enablement of colon cancer stem-like cells. Furthermore, it defines the mechanism of action of RBM5- AS1 in the WNT pathway via physical interactions with b-catenin, helping organize transcriptional complexes that sustain colon CIC function.
UR - http://www.scopus.com/inward/record.url?scp=84989924138&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-15-1824
DO - 10.1158/0008-5472.CAN-15-1824
M3 - Article
C2 - 27520449
AN - SCOPUS:84989924138
SN - 0008-5472
VL - 76
SP - 5615
EP - 5627
JO - Cancer Research
JF - Cancer Research
IS - 19
ER -