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Differences in Transcriptomic Profiles of Brain and Thyroid Tumors with NTRK Gene Rearrangement

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For tumors with chimeric NTRK genes, entrectinib and larotrectinib can be prescribed regardless of tumor localization. We compared changes in the transcriptional activity of genes in brain tumors (BT) and thyroid cancer (TC) with rearrangement (NTRK+) and without rearrangement (NTRK-) of the NTRK genes using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We revealed an increase in the transcription of the JUN gene in NTRK+ samples in comparison with NTRK- samples: by 1.6 times for BT (p=0.239) and by 2.5 times for TC (p=0.003). The transcription of eight HOX genes in NTRK+ BT samples was also increased (by 85-725 times, p<0.05) in comparison with NTRK-. In NTRK+ TC samples, the level of miR-31 and miR-542 was statistically significantly higher (by 3 and 2.5 times, respectively) than in NTRK-samples. For the NTRK+ BT samples, the levels of miR-10b, miR-182, and miR-21 more than 5-fold surpassed the corresponding values in NTRK-samples (p<0.05). These findings reflect differences in activation of gene transcription resulting from NTRK gene rearrangement in BT and TC.

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References

  1. Arévalo JC, Wu SH. Neurotrophin signaling: many exciting surprises! Cell. Mol. Life Sci. 2006;63(13):1523-1537. doi: https://doi.org/10.1007/s00018-006-6010-1

    Article  CAS  PubMed  Google Scholar 

  2. Vaishnavi A, Le AT, Doebele RC. TRKing down an old oncogene in a new era of targeted therapy. Cancer Discov. 2015;5(1):25-34. doi: https://doi.org/10.1158/2159-8290.CD-14-0765

    Article  CAS  PubMed  Google Scholar 

  3. Kechin A, Borobova V, Kel A, Ivanov A, Filipenko M. ErbB4 Is a Potential Key Regulator of the Pathways Activated by NTRK-Fusions in Thyroid Cancer. Appl. Sci. 2022;12(5):2506. doi: https://doi.org/10.3390/app12052506

    Article  CAS  Google Scholar 

  4. Suntsova M, Gaifullin N, Allina D, Reshetun A, Li X, Mendeleeva L, Surin V, Sergeeva A, Spirin P, Prassolov V, Morgan A, Garazha A, Sorokin M, Buzdin A. Atlas of RNA sequencing profiles for normal human tissues. Sci. Data. 2019;6(1):36. doi: https://doi.org/10.1038/s41597-019-0043-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550. doi: https://doi.org/10.1186/s13059-014-0550-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gazon H, Barbeau B, Mesnard JM, Peloponese JM Jr. Hijacking of the AP-1 Signaling Pathway during Development of ATL. Front. Microbiol. 2018;8:2686. doi: https://doi.org/10.3389/fmicb.2017.02686

    Article  PubMed  PubMed Central  Google Scholar 

  7. Pramanik R, Qi X, Borowicz S, Choubey D, Schultz RM, Han J, Chen G. p38 isoforms have opposite effects on AP-1-dependent transcription through regulation of c-Jun. The determinant roles of the isoforms in the p38 MAPK signal specificity. J. Biol. Chem. 2003;278(7):4831-4839. doi: https://doi.org/10.1074/jbc.M207732200

  8. Chen SL, Lin ST, Tsai TC, Hsiao WC, Tsao YP. ErbB4 (JM-b/CYT-1)-induced expression and phosphorylation of c-Jun is abrogated by human papillomavirus type 16 E5 protein. Oncogene. 2007;26(1):42-53. doi: https://doi.org/10.1038/sj.onc.1209768

    Article  CAS  PubMed  Google Scholar 

  9. Gonçalves CS, Le Boiteux E, Arnaud P, Costa BM. HOX gene cluster (de)regulation in brain: from neurodevelopment to malignant glial tumours. Cell. Mol. Life Sci. 2020;77(19):3797-3821. doi: https://doi.org/10.1007/s00018-020-03508-9

    Article  CAS  PubMed  Google Scholar 

  10. Deforzh E, Uhlmann EJ, Das E, Galitsyna A, Arora R, Saravanan H, Rabinovsky R, Wirawan AD, Teplyuk NM, El Fatimy R, Perumalla S, Jairam A, Wei Z, Mirny L, Krichevsky AM. Promoter and enhancer RNAs regulate chromatin reorganization and activation of miR-10b/HOXD locus, and neoplastic transformation in glioma. Mol. Cell. 2022;82(10):1894-1908.e5. doi: https://doi.org/10.1016/j.molcel.2022.03.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wang C, Wang Y, Xu W, Lin X, Xi J, Wang S, Lin L, Yuan F, Wang A, Wang C, Luo X, Xu Q, Yin R, Zhang Y, Huang X, Chen Y. Generation of an induced pluripotent stem cell line from an Ohtahara syndrome patient with the hemizygous mutation p.Q503Afs*28 (c.1507_1508del) in the ARX gene. Stem Cell Res. 2021;59:102621. doi: https://doi.org/10.1016/j.scr.2021.102621

  12. Wei S, Li J, Tang M, Zhang K, Gao X, Fang L, Liu W. STAT3 and p63 in the Regulation of Cancer Stemness. Front. Genet. 2022;13:909251. doi: https://doi.org/10.3389/fgene.2022.909251

  13. Long S, Wang J, Weng F, Xiang D, Sun G. Extracellular Matrix Protein 1 Regulates Colorectal Cancer Cell Proliferative, Migratory, Invasive and Epithelial-Mesenchymal Transition Activities Through the PI3K/AKT/GSK3β/Snail Signaling Axis. Front. Oncol. 2022;12:889159. doi: https://doi.org/10.3389/fonc.2022.889159

  14. Yu T, Ma P, Wu D, Shu Y, Gao W. Functions and mechanisms of microRNA-31 in human cancers. Biomed. Pharmacother. 2018;108:1162-1169. doi: https://doi.org/10.1016/j.biopha.2018.09.132

    Article  CAS  PubMed  Google Scholar 

  15. Yang C, Wang MH, Zhou JD, Chi Q. Upregulation of miR-542-3p inhibits the growth and invasion of human colon cancer cells through PI3K/AKT/survivin signaling. Oncol. Rep. 2017;38(6):3545-3553. doi: https://doi.org/10.3892/or.2017.6054

    Article  CAS  PubMed  Google Scholar 

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Correspondence to A. A. Kechin.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 175, No. 1, pp. 91-99, January, 2023

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Kechin, A.A., Koryukov, M.A., Smertina, M.A. et al. Differences in Transcriptomic Profiles of Brain and Thyroid Tumors with NTRK Gene Rearrangement. Bull Exp Biol Med 175, 78–85 (2023). https://doi.org/10.1007/s10517-023-05815-0

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