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. 2019 Sep 10;20(18):4460.
doi: 10.3390/ijms20184460.

MicroRNA Biogenesis Pathway Genes Are Deregulated in Colorectal Cancer

Petra Vychytilova-Faltejskova  1 , Alena Svobodova Kovarikova  2 , Tomas Grolich  3   4 , Vladimir Prochazka  5   6 , Katerina Slaba  7 , Tana Machackova  8 , Jana Halamkova  9 , Marek Svoboda  10   11   12 , Zdenek Kala  13   14 , Igor Kiss  15   16 , Ondrej Slaby  17   18   19   20
Affiliations

MicroRNA Biogenesis Pathway Genes Are Deregulated in Colorectal Cancer

Petra Vychytilova-Faltejskova et al. Int J Mol Sci. .

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. Each step of their production and maturation has to be strictly regulated, as any disruption of control mechanisms may lead to cancer. Thus, we have measured the expression of 19 genes involved in miRNAs biogenesis pathway in tumor tissues of 239 colorectal cancer (CRC) patients, 17 CRC patients with liver metastases and 239 adjacent tissues using real-time PCR. Subsequently, the expression of analyzed genes was correlated with the clinical-pathological features as well as with the survival of patients. In total, significant over-expression of all analyzed genes was observed in tumor tissues as well as in liver metastases except for LIN28A/B. Furthermore, it was shown that the deregulated levels of some of the analyzed genes significantly correlate with tumor stage, grade, location, size and lymph node positivity. Finally, high levels of DROSHA and TARBP2 were associated with shorter disease-free survival, while the over-expression of XPO5, TNRC6A and DDX17 was detected in tissues of patients with shorter overall survival and poor prognosis. Our data indicate that changed levels of miRNA biogenesis genes may contribute to origin as well as progression of CRC; thus, these molecules could serve as potential therapeutic targets.

Keywords: RT-qPCR; biogenesis; colorectal cancer; disease-free survival; microRNA; overall survival.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Kaplan-Meier survival analysis. High expression of DROSHA (a), EIF2C4 (b) and TARBP2 (c) is associated with significantly shorter disease-free survival (DFS) of CRC patients (p < 0.05). (d-i) Over-expression of DDX17 (d), DICER1 (e), DROSHA (f), EIF2C3 (g), TNRC6A (h), and XPO5 (i) was observed in CRC patients with significantly shorter overall survival (OS) (p < 0.05).
Figure 2
Figure 2
Combined Kaplan-Meier survival analysis. (a) The CRC patients with high expression of TARBP2 and/or DROSHA had significantly shorter DFS compared to patients with low levels of these genes (p = 0.0094). (b) The CRC patients with high levels of XPO5 and/or TNRC6A and/or DDX17 had significantly shorter OS compared to patients with low levels of these genes (p = 0.0004).
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References

    1. Lee R.C., Feinbaum R.L., Ambros V., The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–854. doi: 10.1016/0092-8674(93)90529-Y. - DOI - PubMed
    1. Friedman R.C., Farh K.K.-H., Burge C.B., Bartel D.P. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2009;19:92–105. doi: 10.1101/gr.082701.108. - DOI - PMC - PubMed
    1. Forman J.J., Legesse-Miller A., Coller H.A. A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence. Proc. Natl. Acad. Sci. USA. 2008;105:14879–14884. doi: 10.1073/pnas.0803230105. - DOI - PMC - PubMed
    1. Bartel D.P. MicroRNAs: Target recognition and regulatory functions. Cell. 2009;136:215–233. doi: 10.1016/j.cell.2009.01.002. - DOI - PMC - PubMed
    1. Lytle J.R., Yario T.A., Steitz J.A. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5’ UTR as in the 3’ UTR. Proc. Natl. Acad. Sci. USA. 2007;104:9667–9672. doi: 10.1073/pnas.0703820104. - DOI - PMC - PubMed