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Review
. 2021 Jan 19;11(1):72.
doi: 10.3390/life11010072.

Cancer, Retrogenes, and Evolution

Klaudia Staszak  1 , Izabela Makałowska  1
Affiliations
Review

Cancer, Retrogenes, and Evolution

Klaudia Staszak et al. Life (Basel). .

Abstract

This review summarizes the knowledge about retrogenes in the context of cancer and evolution. The retroposition, in which the processed mRNA from parental genes undergoes reverse transcription and the resulting cDNA is integrated back into the genome, results in additional copies of existing genes. Despite the initial misconception, retroposition-derived copies can become functional, and due to their role in the molecular evolution of genomes, they have been named the "seeds of evolution". It is convincing that retrogenes, as important elements involved in the evolution of species, also take part in the evolution of neoplastic tumors at the cell and species levels. The occurrence of specific "resistance mechanisms" to neoplastic transformation in some species has been noted. This phenomenon has been related to additional gene copies, including retrogenes. In addition, the role of retrogenes in the evolution of tumors has been described. Retrogene expression correlates with the occurrence of specific cancer subtypes, their stages, and their response to therapy. Phylogenetic insights into retrogenes show that most cancer-related retrocopies arose in the lineage of primates, and the number of identified cancer-related retrogenes demonstrates that these duplicates are quite important players in human carcinogenesis.

Keywords: cancer; retrogenes; retroposition; species evolution; tumor evolution.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic view of the relationship between retrogenes, cancer, and evolution.
Figure 2
Figure 2
Mechanism of retrocopy formation (a) and possible functions in the cell (b) (based on mechanisms collectively described by Kubiak et al. [3]).
Figure 3
Figure 3
Evolutionary cancer mechanisms in the context of species-specific features in cancer suppression (a), clonal subpopulations within a tumor (b), and cancer treatment (c).
Figure 4
Figure 4
Cancer-related retrocopies as miRNA sponges in normal and cancer cells. Binding miRNAs to the highly expressed retrogene and translation of the suppressor gene (a). Degradation of the oncogene mRNA by miRNAs binding due to a low retrogene expression (b). Degradation of the suppressor gene mRNA by miRNAs binding because of low retrogene level (c). Binding miRNAs to the high expressed retrogene and translation of the oncogene (d).
Figure 5
Figure 5
Schematic tree illustrating the estimated time of the origin of cancer-related retrocopies during animal evolution.
See this image and copyright information in PMC

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References

    1. Brosius J. Retroposons—Seeds of evolution. Science. 1991;251:753. doi: 10.1126/science.1990437. - DOI - PubMed
    1. Brosius J. The contribution of RNAs and retroposition to evolutionary novelties. Genetica. 2003;118:99–115. doi: 10.1023/A:1024141306559. - DOI - PubMed
    1. Kubiak M.R., Makałowska I. Protein-coding genes’ retrocopies and their functions. Viruses. 2017;9:80. doi: 10.3390/v9040080. - DOI - PMC - PubMed
    1. Kalyana-Sundaram S., Kumar-Sinha C., Shankar S., Robinson D.R., Wu Y.M., Cao X., Asangani I.A., Kothari V., Prensner J.R., Lonigro R.J., et al. Expressed pseudogenes in the transcriptional landscape of human cancers. Cell. 2012;149:1622–1634. doi: 10.1016/j.cell.2012.04.041. - DOI - PMC - PubMed
    1. Han L., Yuan Y., Zheng S., Yang Y., Li J., Edgerton M.E., Diao L., Xu Y., Verhaak R.G.W., Liang H. The Pan-Cancer analysis of pseudogene expression reveals biologically and clinically relevant tumour subtypes. Nat. Commun. 2014;5:3963. doi: 10.1038/ncomms4963. - DOI - PMC - PubMed

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