β-Catenin Regulates Multiple Steps of RNA Metabolism as Revealed by the RNA Aptamer in Colon Cancer Cells

Abstract

Nuclear B-catenin forms a transcription complex with TCF-4, which is implicated in colon cancer development and progression. Recently, we and others have shown that B-catenin could be a regulator of RNA splicing and it also stabilizes the cyclooxygenase-2 (COX-2) mRNA. Here, we further explored the role of B-catenin in the RNA metabolism in colon cancer cells. To specifically modulate the subcellular functions of B-catenin, we expressed the RNA aptamer in the form of RNA intramers with unique cellular localizations. The nucleus-expressed RNA intramer proved to be effective in reducing the protein-protein interaction between B-catenin and TCF-4, thus shown to be a specific regulator of B-cateninactivated transcription. It could also regulate the alternative splicing of E1A minigene in diverse colon cancer cell lines. In addition, we tested whether B-catenin could stabilize any other mRNAs and found that cyclin D1 mRNA was also bound and stabilized by B-catenin. Significantly, the cytoplasmexpressed RNA intramer reverted the B-catenin-induced COX-2 and cyclin D1 mRNA stabilization. We show here that B-catenin regulated multiple steps of RNA metabolism in colon cancer cells and might be the protein factor coordinating RNA metabolism. We suggest that the RNA intramers could provide useful ways for inhibiting B-catenin-mediated transcription and RNA metabolism, which might further enhance the antitumorigenic effects of these molecules in colon cancer cells. [Cancer Res 2007;67(19):9315-21]

The β-catenin/TCF4 pathway modifies alternative splicing through modulation of SRp20 expression

“…The diagram shows the fold-increase following transfection of DLD-1 cells with different SR proteins, and the two RT-PCR gel images show amplicons 11-FP as well as Pol II as control amplification. transcript, the estrogen receptor variant D5-6, and splice variants WISP1v and FGFR3 AT-II (Sato et al 2005;Lee et al 2006Lee et al , 2007. In these cases, the b-catenin/TCF4 complex apparently regulated the expression level of another splicing factor, SF1, and thus affected a different set of splicing events (Shitashige et al 2007).…”

Emerging roles of RNA and RNA-binding protein network in cancer cells

“…In addition, overexpression and unregulated expression of β-catenin regulates RNA alternative splicing and RNA stabilization in colon cancer cells (48)(49)(50). Overexpressed β-catenin upregulates cyclinD1 and c-myc mRNA transcription as transcription factors in cancer cells.…”

IMPs: an RNA-binding protein family that provides a link between stem cell maintenance in normal development and cancer

“…RBPs with a recognized role in tumor growth and progression include the TET family (Riggi et al 2007), the STAR family (Elliott and Rajan 2010), β-catenin (Lee et al 2007;Kim et al 2012), LIN28A and LIN28B Nguyen et al 2014), and several RBPs involved in RNA splicing (David and Manley 2010). Recent work from several laboratories has shown that the IMP family of oncofetal RBPs can promote carcinogenesis in part by regulating miRNA activity.…”