Functionality of Intron-Specific Genes and Cancer Stem Cells in the Progression of Colorectal Cancer

  • Janani Gopi
  • Madhumala Gopinath
  • Xiao-Feng Sun
  • Surajit PathakEmail author
  • Antara Banerjee


This review article deals with comprehensive information about the evolutionary history of introns with their localization and functions in the gene transcripts of colorectal cancer precisely. In this way, the major breakthrough in the molecular biology discipline was the discovery of introns by Richard Robert and Phil Sharp in 1977. Firstly, noncoding regions are recognized by various assortments of regulatory ncRNA sequences such as circular RNA, telomere-associated RNA, small nuclear RNA, Piwi-interacting RNA, small interfering RNA, small nucleolar RNA, microRNA, and long noncoding RNA. Fortunately, splicing process of mRNA strand deals with the excision of introns via spliceosomal proteins into mature mRNA which is witnessed only in eukaryotic organisms and devoid of the splicing machinery components in the prokaryotic organisms. The major focal point relies on intronic genes mainly involved in the progression of colorectal cancer with preliminary information. An alternative splicing process takes place in mRNA that implicates in intron retention leading to varied gene expression in cells and tissues and their promotion in colorectal cancer. Therefore, colorectal cancer-associated diseases have paved the way to know more about the intronic genes mainly concentrated among them in the progression of the related diseases. Hence, the focus of the researchers is toward the fascinating cellular and molecular biology aspects of the regulatory intronic sequences known to enhance as well as repress particular gene expression in tumor microenvironment of colorectal cancer by analyzing the genome and proteome levels for the betterment of human kind that is intended for various therapeutic purposes.


Introns (noncoding sequences) mRNA Spliceosomal proteins Alternate splicing process Intron retention Colorectal cancer 



The authors are thankful to Science and Engineering Research Board (SERB) (EMR/20l7/001877) for providing the Core Research Grant to Prof. Surajit Pathak and Chettinad Academy of Research and Education for the research support.


  1. 1.
    Chorev M, Carmel L (2012) The function of introns. Front Genet 3:55CrossRefGoogle Scholar
  2. 2.
    Niu D-K, Yang Y-F (2011) Why eukaryotic cells use introns to enhance gene expression: splicing reduces transcription associated mutagenesis by inhibiting topoisomerase I cutting activity. Biol Direct 6:24CrossRefGoogle Scholar
  3. 3.
    Jeffares DC, Mourier T, Penny D (2006) The biology of intron gain and loss. Trends Genet 22(1):16–22CrossRefGoogle Scholar
  4. 4.
    Haugen P, Simon DM, Bhattacharya D (2005) The natural history of group I introns. Trends Genet 21(2):111–119CrossRefGoogle Scholar
  5. 5.
    Irimia M, Roy SW (2014) Origin of spliceosomal introns and alternative splicing. Cold Spring Harb Perspect Biol 6(6):a016071CrossRefGoogle Scholar
  6. 6.
    Middleton R, Gao D, Thomas A et al (2017) Irfinder: assessing the impact of intron retention on mammalian gene expression. Genome Biol 18(1):51CrossRefGoogle Scholar
  7. 7.
    Esquela-Kerscher A, Slack FJ (2006) Oncomirs – microRNAs with a role in cancer. Nat Rev Cancer 6(4):259–269CrossRefGoogle Scholar
  8. 8.
    Lizarbe MA, Fernández-Lizarbe S, Calle-Espinosa J et al (2017) Colorectal cancer: from the genetic model to posttranscriptional regulation by noncoding RNAs. Hindawi Biomed Res Int 2017:7354260Google Scholar
  9. 9.
    Cheetham SW, Gruhl F, Mattick JS, Dinger ME (2013) Long noncoding rnas and the genetics of cancer. Br J Cancer 108:2419–2425CrossRefGoogle Scholar
  10. 10.
    Alhopuro P, Sammalkorpi H et al (2011) Candidate driver genes in microsatellite-unstable colorectal cancer. Int J Cancer 130(7):1558–1566CrossRefGoogle Scholar
  11. 11.
    Sameer AS (2013) Colorectal cancer: molecular mutations and polymorphisms. Front Oncol 3:114CrossRefGoogle Scholar
  12. 12.
    Jung H, Lee D, Lee J et al (2015) Intron retention is a widespread mechanism of tumor-suppressor inactivation. Nat Genet 47(11):1242–1248CrossRefGoogle Scholar
  13. 13.
    Dvinge H, Bradley RK (2015) Widespread intron retention diversifies most cancer transcriptomes. Genome Med 7:45CrossRefGoogle Scholar
  14. 14.
    Wong JJ-L, Au AYM et al (2015) Intron retention in mRNA: no longer nonsense. Bioessays 38:41–49CrossRefGoogle Scholar
  15. 15.
    Fang X et al (2016) SNORD126 promotes HCC and CRC cell growth by activating the PI3K-AKT pathway through FGFR2. J Mol Cell Biol Adv 9(3):243–255Google Scholar
  16. 16.
    Wong JJ-L et al (2015) Intron retention in mRNA: no longer nonsense. Bioessays 38:41–49CrossRefGoogle Scholar
  17. 17.
    Middleton R et al (2017) IRFinder: assessing the impact of intron retention on mammalian gene expression. Genome Biol 18:51CrossRefGoogle Scholar
  18. 18.
    Buckley PT (2014) Cytoplasmic intron retention, function, splicing, and the sentinel RNA hypothesis. WIREs RNA 5:223–230CrossRefGoogle Scholar
  19. 19.
    Martinez-Montiel N et al (2018) Alternative splicing as a target for cancer treatment. Int J Mol Sci 19:545CrossRefGoogle Scholar
  20. 20.
    Steiman-Shimony A et al (2018) Assessing the functional association of intronic mirnas with their host genes. RNA 24:991–1004CrossRefGoogle Scholar
  21. 21.
    Abebrese EL et al (2017) Identification of human short introns. PLoS One 12(5):e0175393CrossRefGoogle Scholar
  22. 22.
    Rohlin A et al (2017) Expanding the genotype–phenotype spectrum in hereditary colorectal cancer by gene panel testing. Fam Cancer 16:195–203CrossRefGoogle Scholar
  23. 23.
    Hube F et al (2017) Short intron-derived ncRNAs. Nucleic Acids Res 45(8):4768–4781PubMedPubMedCentralGoogle Scholar
  24. 24.
    Schmitz U et al (2017) Intron retention enhances gene regulatory complexity in vertebrates. Genome Biol 18:216CrossRefGoogle Scholar
  25. 25.
    Bartonicek N et al (2017) Intergenic disease-associated regions are abundant in novel transcripts. Genome Biol 18:241CrossRefGoogle Scholar
  26. 26.
    Roy S et al (2012) Cancer stem cells in colorectal cancer: genetic and epigenetic changes. J Stem Cell Res Ther 7(Suppl 6):10342PubMedGoogle Scholar
  27. 27.
    Kim SW et al (2017) Widespread intra-dependencies in the removal of introns from human transcripts. Nucleic Acids Res 45(16):9503–9513CrossRefGoogle Scholar
  28. 28.
    Munro MJ et al (2017) Cancer stem cells in colorectal cancer: a review. J Clin Pathol 71(2):110–116CrossRefGoogle Scholar
  29. 29.
    Huang T et al (2013) Noncoding RNAs in cancer and cancer stem cells. Chin J Cancer 32:582–593CrossRefGoogle Scholar
  30. 30.
    Zhou Y et al (2018) Cancer stem cells in progression of colorectal cancer. Oncotarget 9(70):33403–33415CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  • Janani Gopi
    • 1
  • Madhumala Gopinath
    • 1
  • Xiao-Feng Sun
    • 2
  • Surajit Pathak
    • 1
    Email author
  • Antara Banerjee
    • 1
  1. 1.Faculty of Allied Health Sciences, Chettinad Academy of Research and EducationChettinad Hospital and Research Institute (CHRI)ChennaiIndia
  2. 2.Department of Oncology and Biomedical and Clinical SciencesLinköping UniversityLinköpingSweden

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