title: Crosstalk between Wnt Signaling and RNA Processing in Colorectal Cancer.
abstract: RNA processing involves a variety of processes affecting gene expression, including the removal of introns through RNA splicing, as well as 3' end processing (cleavage and polyadenylation). Alternative RNA processing is fundamentally important for gene regulation, and aberrant processing is associated with the initiation and progression of cancer. Deregulated Wnt signaling, which is the initiating event in the development of most cases of human colorectal cancer (CRC), has been linked to modified RNA processing, which may contribute to Wnt-mediated colonic carcinogenesis. Crosstalk between Wnt signaling and alternative RNA splicing with relevance to CRC includes effects on the expression of Rac1b, an alternatively spliced gene associated with tumorigenesis, which exhibits alternative RNA splicing that is influenced by Wnt activity. In addition, Tcf4, a crucial component of Wnt signaling, also exhibits alternative splicing, which is likely involved in colonic tumorigenesis. Modulation of 3' end formation, including of the Wnt target gene COX-2, also can influence the neoplastic process, with implications for CRC. While many human genes are dependent on introns and splicing for normal levels of gene expression, naturally intronless genes exist with a unique metabolism that allows for intron-independent gene expression. Effects of Wnt activity on the RNA metabolism of the intronless Wnt-target gene c-jun is a likely contributor to cancer development. Further, butyrate, a breakdown product of dietary fiber and a histone deacetylase inhibitor, upregulates Wnt activity in CRC cells, and also modulates RNA processing; therefore, the interplay between Wnt activity, the modulation of this activity by butyrate, and differential RNA metabolism in colonic cells can significantly influence tumorigenesis. Determining the role played by altered RNA processing in Wnt-mediated neoplasia may lead to novel interventions aimed at restoring normal RNA metabolism for therapeutic benefit. Therefore, this minireview presents a brief overview of several aspects of RNA processing of relevance to cancer, which potentially influence, or are influenced by, Wnt signaling activity.
authors: Department of Basic Sciences, The Commonwealth Medical College, 525 Pine Street, Scranton, PA 18509, USA.
authors: Michael
authors: M
authors: Bordonaro
keywords: RNA processing; Wnt activity; butyrate; colon cancer; polyadenylation.; splicing
references: Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9808-13
references: 11504946
references: Inflammopharmacology. 2005;13(1-3):113-25
references: 16259733
references: Int J Cancer. 2004 Jul 1;110(4):523-31
references: 15122584
references: Blood. 2009 Nov 5;114(19):4179-85
references: 19745069
references: Exp Cell Res. 2009 Oct 1;315(16):2752-64
references: 19577565
references: FEBS Lett. 2006 Aug 7;580(18):4303-5
references: 16842783
references: Proc Nutr Soc. 1990 Jul;49(2):153-71
references: 2172992
references: Gastroenterology. 2005 Oct;129(4):1225-36
references: 16230076
references: JPEN J Parenter Enteral Nutr. 1996 Jul-Aug;20(4):243-50
references: 8865104
references: Trends Genet. 2008 Aug;24(8):375-8
references: 18586348
references: Mol Cell. 2011 Aug 5;43(3):327-39
references: 21723170
references: Mol Cell Biol. 2008 Dec;28(24):7368-79
references: 18852287
references: Nucleic Acids Res. 2002 Oct 15;30(20):e109
references: 12384611
references: Nucleic Acids Res. 2006;34(19):5705-14
references: 17040897
references: Exp Cell Res. 2007 May 1;313(8):1652-66
references: 17359971
references: Cancer Res. 1995 Aug 15;55(16):3537-42
references: 7627961
references: Cancer Res. 1992 Nov 1;52(21):5906-12
references: 1327519
references: Cancer Res. 1995 Nov 15;55(22):5226-9
references: 7585580
references: Cancer Res. 2007 Mar 15;67(6):2469-79
references: 17363564
references: Cancer Res. 2009 Dec 15;69(24):9422-30
references: 19934316
references: Nucleic Acids Res. 2004 Jun 04;32(10):3108-14
references: 15181176
references: Cancer Res. 2007 Oct 1;67(19):9315-21
references: 17909039
references: Cancer Res. 1994 Jun 15;54(12):3288-93
references: 8205551
references: OMICS. 2006 Fall;10(3):344-57
references: 17069512
references: Gene Ther. 2004 Jan;11(2):187-93
references: 14712303
references: J Pharmacol Sci. 2007 May;104(1):19-28
references: 17510524
references: Hum Mol Genet. 2009 Oct 15;18(20):3795-804
references: 19602480
references: Cancer Res. 1997 Sep 1;57(17):3697-707
references: 9288776
references: BMB Rep. 2009 Jun 30;42(6):356-60
references: 19558794
references: Biochem Biophys Res Commun. 2005 Dec 2;337(4):1192-7
references: 16229817
references: Bioinformatics. 2002 Sep;18(9):1266-7
references: 12217920
references: Diabetologia. 2011 Dec;54(12):3078-82
references: 21913056
references: Oncogene. 2008 Oct 16;27(47):6151-63
references: 18641687
references: Nucleic Acids Res. 2012 Aug;40(14):6863-72
references: 22544606
references: FEBS Lett. 2007 Oct 16;581(25):4850-6
references: 17888911
references: Nucleic Acids Res. 1990 Jun 25;18(12):3605-10
references: 2114014
references: Endocrinology. 2010 Apr;151(4):1391-7
references: 20332203
references: EMBO J. 2009 Jul 8;28(13):1843-54
references: 19521338
references: Proteomics. 2012 Jun;12(12):2045-59
references: 22623141
references: J Mol Med (Berl). 1996 Dec;74(12):725-47
references: 8974016
references: Mol Biol Rep. 2010 Jun;37(5):2415-21
references: 19693690
references: Biochem Biophys Res Commun. 2005 Jun 3;331(2):512-9
references: 15850789
references: Nucleic Acids Res. 2005 Apr 20;33(7):2215-26
references: 15843684
references: Cell. 2009 Aug 21;138(4):673-84
references: 19703394
references: Mol Carcinog. 2004 Dec;41(4):187-96
references: 15390079
references: Cancer Res. 1988 Apr 15;48(8):2096-100
references: 3258183
references: Hum Mol Genet. 2009 Oct 1;18(19):3696-707
references: 19602482
references: Cancer Res. 2006 Nov 1;66(21):10560-6
references: 17079480
references: Methods Enzymol. 2006;410:300-16
references: 16938557
references: Carcinogenesis. 1995 May;16(5):1199-205
references: 7767986
references: Cell Growth Differ. 1999 Oct;10(10):713-20
references: 10547075
references: Science. 1997 Mar 21;275(5307):1784-7
references: 9065401
references: Cell Res. 2007 Jul;17(7):581-90
references: 17621309
references: Science. 1987 Dec 4;238(4832):1386-92
references: 2825349
references: Nucleic Acids Res. 2005 May 04;33(8):2565-79
references: 15872218
references: FEBS Lett. 1993 Aug 16;328(3):225-9
references: 8348968
references: BMC Biol. 2010 Jul 08;8:95
references: 20619007