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RBM5-AS1 Is Critical for Self-Renewal of Colon Cancer Stem-like Cells.

ABSTRACT: 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 ?-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 ?-catenin. Mechanistic investigations showed that silencing or overexpression of RBM5-AS1 caused a respective loss or retention of ?-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 ?-catenin, helping organize transcriptional complexes that sustain colon CIC function. Cancer Res; 76(19); 5615-27. ©2016 AACR.

SUBMITTER: Di Cecilia S

PROVIDER: S-EPMC5050123 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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RBM5-AS1 Is Critical for Self-Renewal of Colon Cancer Stem-like Cells.

Di Cecilia Serena S Zhang Fan F Sancho Ana A Li SiDe S Aguiló Francesca F Sun Yifei Y Rengasamy Madhumitha M Zhang Weijia W Del Vecchio Luigi L Salvatore Francesco F Walsh Martin J MJ

Cancer research 20160812 19

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 β-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 format ...[more]

PMID: 27520449

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RBM5-AS1 Is Critical for Self-Renewal of Colon Cancer Stem-like Cells.

Publications

RBM5-AS1 Is Critical for Self-Renewal of Colon Cancer Stem-like Cells.

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