Alternative Splicing of DNA Damage Response Genes and Gastrointestinal Cancers

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2014 Dec 18

PMID 25516641

Citations 11

Authors

Bahityar Rahmutulla

Kazuyuki Matsushita

Fumio Nomura

Affiliations

Soon will be listed here.

Abstract

Alternative splicing, which is a common phenomenon in mammalian genomes, is a fundamental process of gene regulation and contributes to great protein diversity. Alternative splicing events not only occur in the normal gene regulation process but are also closely related to certain diseases including cancer. In this review, we briefly demonstrate the concept of alternative splicing and DNA damage and describe the association of alternative splicing and cancer pathogenesis, focusing on the potential relationship of alternative splicing, DNA damage, and gastrointestinal cancers. We will also discuss whether alternative splicing leads to genetic instability, which is considered to be a driving force for tumorigenesis. Better understanding of the role and mechanism of alternative splicing in tumorigenesis may provide new directions for future cancer studies.

Citing Articles

The RNA-binding protein LARP6 regulates the alternative splicing of related genes in MDA-MB-231 cells.

Guo L, Liu Y, Yan S, Li H, Zhang K, Li J Sci Rep. 2025; 15(1):7883.

PMID: 40050364 PMC: 11885556. DOI: 10.1038/s41598-025-92351-8.

Importance of pre-mRNA splicing and its study tools in plants.

Liu Y, Do S, Huynh H, Li J, Liu Y, Du Z Adv Biotechnol (Singap). 2025; 2(1):4.

PMID: 39883322 PMC: 11740881. DOI: 10.1007/s44307-024-00009-9.

Multi-omics Analyses Reveal Function of Apolipoprotein E in Alternative Splicing and Tumor Immune Microenvironment in Kidney Renal Clear Cell Carcinoma via Pan-cancer Analysis.

Leng X, Liu J, Jin A, Zheng H, Wu J, Zhong L Cell Biochem Biophys. 2024; 82(1):1-13.

PMID: 38182861 DOI: 10.1007/s12013-023-01211-7.

A Novel Nomogram Combining Alternative Splicing Events and Clinical Factors for Prognosis Prediction in Head and Neck Squamous Cell Carcinoma.

Jiang J, Niu L, Zhang M, Wang H, Xie J, Sun G J Oncol. 2022; 2022:4552445.

PMID: 35103061 PMC: 8800633. DOI: 10.1155/2022/4552445.

Prognostic Alternative Splicing Signatures in Esophageal Carcinoma.

Dlamini Z, Hull R, Mbatha S, Alaouna M, Qiao Y, Yu H Cancer Manag Res. 2021; 13:4509-4527.

PMID: 34113176 PMC: 8186946. DOI: 10.2147/CMAR.S305464.

References

De Vogelaere K, Aerts M, Haentjens P, De Greve J, Delvaux G . Gastrointestinal stromal tumor of the stomach: progresses in diagnosis and treatment. Acta Gastroenterol Belg. 2014; 76(4):403-6. View

Matsushita K, Tomonaga T, Kajiwara T, Shimada H, Itoga S, Hiwasa T . c-myc suppressor FBP-interacting repressor for cancer diagnosis and therapy. Front Biosci (Landmark Ed). 2009; 14(9):3401-8. DOI: 10.2741/3461. View

Avigan M, Strober B, Levens D . A far upstream element stimulates c-myc expression in undifferentiated leukemia cells. J Biol Chem. 1990; 265(30):18538-45. View

Guo W, Frenette P . Alternative CD44 splicing in intestinal stem cells and tumorigenesis. Oncogene. 2013; 33(5):537-8. DOI: 10.1038/onc.2013.260. View

Sultan M, Schulz M, Richard H, Magen A, Klingenhoff A, Scherf M . A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome. Science. 2008; 321(5891):956-60. DOI: 10.1126/science.1160342. View

Lord C, Ashworth A . Mechanisms of resistance to therapies targeting BRCA-mutant cancers. Nat Med. 2013; 19(11):1381-8. DOI: 10.1038/nm.3369. View

Malz M, Bovet M, Samarin J, Rabenhorst U, Sticht C, Bissinger M . Overexpression of far upstream element (FUSE) binding protein (FBP)-interacting repressor (FIR) supports growth of hepatocellular carcinoma. Hepatology. 2014; 60(4):1241-50. DOI: 10.1002/hep.27218. View

Giannini G, Ristori E, Cerignoli F, Rinaldi C, Zani M, Viel A . Human MRE11 is inactivated in mismatch repair-deficient cancers. EMBO Rep. 2002; 3(3):248-54. PMC: 1084012. DOI: 10.1093/embo-reports/kvf044. View

Schultz N, Lopez E, Saleh-Gohari N, Helleday T . Poly(ADP-ribose) polymerase (PARP-1) has a controlling role in homologous recombination. Nucleic Acids Res. 2003; 31(17):4959-64. PMC: 212803. DOI: 10.1093/nar/gkg703. View

10.

Modrek B, Lee C . A genomic view of alternative splicing. Nat Genet. 2001; 30(1):13-9. DOI: 10.1038/ng0102-13. View

11.

Lokody I . Alternative splicing: aberrant splicing promotes colon tumour growth. Nat Rev Cancer. 2014; 14(6):382-3. DOI: 10.1038/nrc3753. View

12.

Kaur G, Saif M . Translational research in pancreatic adenocarcinoma. JOP. 2014; 15(2):121-3. DOI: 10.6092/1590-8577/2327. View

13.

Hermeking H . MicroRNAs in the p53 network: micromanagement of tumour suppression. Nat Rev Cancer. 2012; 12(9):613-26. DOI: 10.1038/nrc3318. View

14.

Collis S, DeWeese T, Jeggo P, Parker A . The life and death of DNA-PK. Oncogene. 2004; 24(6):949-61. DOI: 10.1038/sj.onc.1208332. View

15.

Nelson L, Bender C, Mannsperger H, Buergy D, Kambakamba P, Mudduluru G . Triplex DNA-binding proteins are associated with clinical outcomes revealed by proteomic measurements in patients with colorectal cancer. Mol Cancer. 2012; 11:38. PMC: 3537547. DOI: 10.1186/1476-4598-11-38. View

16.

Sanz D, Acedo A, Infante M, Duran M, Perez-Cabornero L, Esteban-Cardenosa E . A high proportion of DNA variants of BRCA1 and BRCA2 is associated with aberrant splicing in breast/ovarian cancer patients. Clin Cancer Res. 2010; 16(6):1957-67. DOI: 10.1158/1078-0432.CCR-09-2564. View

17.

Reichert M, Takano S, von Burstin J, Kim S, Lee J, Ihida-Stansbury K . The Prrx1 homeodomain transcription factor plays a central role in pancreatic regeneration and carcinogenesis. Genes Dev. 2013; 27(3):288-300. PMC: 3576514. DOI: 10.1101/gad.204453.112. View

18.

Je E, Yoo N, Kim Y, Kim M, Lee S . Mutational analysis of splicing machinery genes SF3B1, U2AF1 and SRSF2 in myelodysplasia and other common tumors. Int J Cancer. 2013; 133(1):260-5. DOI: 10.1002/ijc.28011. View

19.

Davies H, Bignell G, Cox C, Stephens P, Edkins S, Clegg S . Mutations of the BRAF gene in human cancer. Nature. 2002; 417(6892):949-54. DOI: 10.1038/nature00766. View

20.

Ewing B, Green P . Analysis of expressed sequence tags indicates 35,000 human genes. Nat Genet. 2000; 25(2):232-4. DOI: 10.1038/76115. View