RBM5-AS1 is critical for self-renewal of colon cancer stem-like cells

Serena Di Cecilia, Fan Zhang, Ana Sancho, Side Li, Francesca Aguilo, Yifei Sun, Madhumitha Rengasamy, Weijia Zhang, Luigi Del Vecchio, Francesco Salvatore, Martin J. Walsh

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


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.

Original languageEnglish
Pages (from-to)5615-5627
Number of pages13
JournalCancer Research
Issue number19
StatePublished - 1 Oct 2016


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