Journal
CANCER RESEARCH
Volume 76, Issue 19, Pages 5615-5627Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-15-1824
Keywords
-
Categories
Funding
- NCI NIH HHS [R01 CA154809] Funding Source: Medline
- NHLBI NIH HHS [R01 HL067099, R01 HL103967] Funding Source: Medline
- NIH HHS [S10 OD018522] Funding Source: Medline
Ask authors/readers for more resources
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 beta-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 nuclear-retained transcript that selectively interacted with beta-catenin. Mechanistic investigations showed that silencing or overexpression of RBM5-AS1 caused a respective loss or retention of beta-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 beta-catenin, helping organize transcriptional complexes that sustain colon CIC function. (C) 2016 AACR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available