Crosstalk Between Wnt Signaling and RNA Processing in Colorectal Cancer

Overview

Journal J Cancer

Specialty Oncology

Date 2013 Feb 7

PMID 23386908

Citations 20

Authors

Michael Bordonaro

Affiliations

Soon will be listed here.

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.

Citing Articles

A Systematic Identification of RNA-Binding Proteins (RBPs) Driving Aberrant Splicing in Cancer.

Lobato-Fernandez C, Gimeno M, San Martin A, Anorbe A, Rubio A, Ferrer-Bonsoms J Biomedicines. 2024; 12(11).

PMID: 39595158 PMC: 11591948. DOI: 10.3390/biomedicines12112592.

Nasal microRNA signatures for disease severity in infants with respiratory syncytial virus bronchiolitis: a multicentre prospective study.

Kyo M, Zhu Z, Shibata R, Ooka T, Mansbach J, Harmon B BMJ Open Respir Res. 2024; 11(1).

PMID: 39089741 PMC: 11293419. DOI: 10.1136/bmjresp-2023-002288.

The Roles of RAC1 and RAC1B in Colorectal Cancer and Their Potential Contribution to Cetuximab Resistance.

Wahoski C, Singh B Cancers (Basel). 2024; 16(13).

PMID: 39001533 PMC: 11240352. DOI: 10.3390/cancers16132472.

GPX2 acts as an oncogene and cudraflavone C has an anti-tumor effect by suppressing GPX2-dependent Wnt/β-catenin pathway in colorectal cancer cells.

Wu Z, Zhou S, Liang D, Mu L Naunyn Schmiedebergs Arch Pharmacol. 2023; 397(2):1115-1125.

PMID: 37610461 DOI: 10.1007/s00210-023-02668-2.

Vitamin D receptor prevents tumour development by regulating the Wnt/β-catenin signalling pathway in human colorectal cancer.

Yu J, Sun Q, Hui Y, Xu J, Shi P, Chen Y BMC Cancer. 2023; 23(1):336.

PMID: 37046222 PMC: 10091620. DOI: 10.1186/s12885-023-10690-z.

References

Chang J, Hsieh-Li H, Jong Y, Wang N, Tsai C, Li H . Treatment of spinal muscular atrophy by sodium butyrate. Proc Natl Acad Sci U S A. 2001; 98(17):9808-13. PMC: 55534. DOI: 10.1073/pnas.171105098. View

Ashida R, Tominaga K, Sasaki E, Watanabe T, Fujiwara Y, Oshitani N . AP-1 and colorectal cancer. Inflammopharmacology. 2005; 13(1-3):113-25. DOI: 10.1163/156856005774423935. View

Lazarova D, Bordonaro M, Carbone R, Sartorelli A . Linear relationship between Wnt activity levels and apoptosis in colorectal carcinoma cells exposed to butyrate. Int J Cancer. 2004; 110(4):523-31. DOI: 10.1002/ijc.20152. View

Sharma S, Lichtenstein A . Aberrant splicing of the E-cadherin transcript is a novel mechanism of gene silencing in chronic lymphocytic leukemia cells. Blood. 2009; 114(19):4179-85. PMC: 2774554. DOI: 10.1182/blood-2009-03-206482. View

Sahota A, Dhoot G . A novel SULF1 splice variant inhibits Wnt signalling but enhances angiogenesis by opposing SULF1 activity. Exp Cell Res. 2009; 315(16):2752-64. DOI: 10.1016/j.yexcr.2009.06.029. View

Hill A, Sorscher E . The non-random distribution of intronless human genes across molecular function categories. FEBS Lett. 2006; 580(18):4303-5. DOI: 10.1016/j.febslet.2006.06.051. View

Bingham S . Mechanisms and experimental and epidemiological evidence relating dietary fibre (non-starch polysaccharides) and starch to protection against large bowel cancer. Proc Nutr Soc. 1990; 49(2):153-71. DOI: 10.1079/pns19900021. View

Sato S, Idogawa M, Honda K, Fujii G, Kawashima H, Takekuma K . Beta-catenin interacts with the FUS proto-oncogene product and regulates pre-mRNA splicing. Gastroenterology. 2005; 129(4):1225-36. DOI: 10.1053/j.gastro.2005.07.025. View

Velazquez O, Zhou D, Seto R, Jabbar A, Choi J, Lederer H . In vivo crypt surface hyperproliferation is decreased by butyrate and increased by deoxycholate in normal rat colon: associated in vivo effects on c-Fos and c-Jun expression. JPEN J Parenter Enteral Nutr. 1996; 20(4):243-50. DOI: 10.1177/0148607196020004243. View

10.

Jeffares D, Penkett C, Bahler J . Rapidly regulated genes are intron poor. Trends Genet. 2008; 24(8):375-8. DOI: 10.1016/j.tig.2008.05.006. View

11.

Mukherjee N, Corcoran D, Nusbaum J, Reid D, Georgiev S, Hafner M . Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability. Mol Cell. 2011; 43(3):327-39. PMC: 3220597. DOI: 10.1016/j.molcel.2011.06.007. View

12.

Yochum G, Cleland R, Goodman R . A genome-wide screen for beta-catenin binding sites identifies a downstream enhancer element that controls c-Myc gene expression. Mol Cell Biol. 2008; 28(24):7368-79. PMC: 2593444. DOI: 10.1128/MCB.00744-08. View

13.

Nasim M, Chowdhury H, Eperon I . A double reporter assay for detecting changes in the ratio of spliced and unspliced mRNA in mammalian cells. Nucleic Acids Res. 2002; 30(20):e109. PMC: 137153. DOI: 10.1093/nar/gnf108. View

14.

Lee H, Jeong S . Beta-Catenin stabilizes cyclooxygenase-2 mRNA by interacting with AU-rich elements of 3'-UTR. Nucleic Acids Res. 2006; 34(19):5705-14. PMC: 1636482. DOI: 10.1093/nar/gkl698. View

15.

Bordonaro M, Lazarova D, Sartorelli A . The activation of beta-catenin by Wnt signaling mediates the effects of histone deacetylase inhibitors. Exp Cell Res. 2007; 313(8):1652-66. PMC: 3919021. DOI: 10.1016/j.yexcr.2007.02.008. View

16.

Bell D, STEPHENS E, Castranio T, Umbach D, Watson M, Deakin M . Polyadenylation polymorphism in the acetyltransferase 1 gene (NAT1) increases risk of colorectal cancer. Cancer Res. 1995; 55(16):3537-42. View

17.

Boffa L, Lupton J, Mariani M, Ceppi M, Newmark H, Scalmati A . Modulation of colonic epithelial cell proliferation, histone acetylation, and luminal short chain fatty acids by variation of dietary fiber (wheat bran) in rats. Cancer Res. 1992; 52(21):5906-12. View

18.

Bell D, Badawi A, Lang N, Ilett K, Kadlubar F, Hirvonen A . Polymorphism in the N-acetyltransferase 1 (NAT1) polyadenylation signal: association of NAT1*10 allele with higher N-acetylation activity in bladder and colon tissue. Cancer Res. 1995; 55(22):5226-9. View

19.

Esufali S, Charames G, Pethe V, Buongiorno P, Bapat B . Activation of tumor-specific splice variant Rac1b by dishevelled promotes canonical Wnt signaling and decreased adhesion of colorectal cancer cells. Cancer Res. 2007; 67(6):2469-79. DOI: 10.1158/0008-5472.CAN-06-2843. View

20.

Singh P, Alley T, Wright S, Kamdar S, Schott W, Wilpan R . Global changes in processing of mRNA 3' untranslated regions characterize clinically distinct cancer subtypes. Cancer Res. 2009; 69(24):9422-30. PMC: 2794997. DOI: 10.1158/0008-5472.CAN-09-2236. View