Display options
Share it on

Sci Rep. 2022 Jan 07;12(1):199. doi: 10.1038/s41598-021-03989-z.

Comprehensive quantitative analysis of alternative splicing variants reveals the HNF1B mRNA splicing pattern in various tumour and non-tumour tissues.

Scientific reports

Jan Hojny, Romana Michalkova, Eva Krkavcova, Quang Hiep Bui, Michaela Bartu, Kristyna Nemejcova, Marta Kalousova, Petra Kleiblova, Pavel Dundr, Ivana Struzinska

Affiliations

  1. Institute of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Studni?kova 2, 12800, Prague 2, Czech Republic.
  2. Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Kate?inská 32, 121 08, Prague 2, Czech Republic.
  3. Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Albertov 4, 128 00, Prague 2, Czech Republic.
  4. Institute of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Studni?kova 2, 12800, Prague 2, Czech Republic. [email protected].

PMID: 34997048 PMCID: PMC8741901 DOI: 10.1038/s41598-021-03989-z

Abstract

Hepatocyte nuclear factor-1-beta (HNF1B) is a transcription factor and putative biomarker of solid tumours. Recently, we have revealed a variety of HNF1B mRNA alternative splicing variants (ASVs) with unknown, but potentially regulatory, functions. The aim of our work was to quantify the most common variants and compare their expression in tumour and non-tumour tissues of the large intestine, prostate, and kidney. The HNF1B mRNA variants 3p, Δ7, Δ7-8, and Δ8 were expressed across all the analysed tissues in 28.2-33.5%, 1.5-2%, 0.8-1.7%, and 2.3-6.9% of overall HNF1B mRNA expression, respectively, and occurred individually or in combination. The quantitative changes of ASVs between tumour and non-tumour tissue were observed for the large intestine (3p, Δ7-8), prostate (3p), and kidney samples (Δ7). Decreased expression of the overall HNF1B mRNA in the large intestine and prostate cancer samples compared with the corresponding non-tumour samples was observed (p = 0.019 and p = 0.047, respectively). The decreased mRNA expression correlated with decreased protein expression in large intestine carcinomas (p < 0.001). The qualitative and quantitative pattern of the ASVs studied by droplet digital PCR was confirmed by next-generation sequencing, which suggests the significance of the NGS approach for further massive evaluation of the splicing patterns in a variety of genes.

© 2022. The Author(s).

References

  1. Dokl Biochem Biophys. 2017 Jul;475(1):250-252 - PubMed
  2. Folia Biol (Praha). 2018;64(3):71-83 - PubMed
  3. Front Genet. 2019 Nov 19;10:1139 - PubMed
  4. PLoS One. 2009 Nov 16;4(11):e7855 - PubMed
  5. Hum Mol Genet. 2004 Dec 15;13(24):3139-49 - PubMed
  6. Sci Rep. 2020 Apr 24;10(1):6958 - PubMed
  7. Lab Invest. 2015 Aug;95(8):962-72 - PubMed
  8. Am J Pathol. 2003 Dec;163(6):2503-12 - PubMed
  9. BMC Cancer. 2010 Jun 22;10:315 - PubMed
  10. Biopreserv Biobank. 2015 Oct;13(5):311-9 - PubMed
  11. Sci Rep. 2020 Oct 13;10(1):17151 - PubMed
  12. Cell Biosci. 2015 Oct 13;5:58 - PubMed
  13. Urol Oncol. 2014 May;32(4):426-32 - PubMed
  14. Gene. 2017 Dec 30;637:41-49 - PubMed
  15. Pathol Oncol Res. 2016 Jul;22(3):523-30 - PubMed
  16. PLoS One. 2010 May 28;5(5):e10858 - PubMed
  17. Pathol Oncol Res. 2020 Oct;26(4):2337-2350 - PubMed
  18. J Clin Invest. 2004 Mar;113(6):913-23 - PubMed
  19. FASEB J. 1996 Feb;10(2):267-82 - PubMed
  20. BMC Cancer. 2016 Aug 12;16:632 - PubMed
  21. Clin Chem. 2013 Jun;59(6):892-902 - PubMed
  22. Nucleic Acids Res. 2016 Jan 4;44(D1):D1018-22 - PubMed
  23. Nat Genet. 2011 May;43(5):451-4 - PubMed
  24. Urology. 2010 Aug;76(2):507.e6-11 - PubMed
  25. Nat Biotechnol. 2011 Jan;29(1):24-6 - PubMed
  26. Hum Pathol. 2007 Jul;38(7):1074-1080 - PubMed
  27. Sci Rep. 2020 Sep 1;10(1):14365 - PubMed
  28. Oncol Lett. 2021 Mar;21(3):185 - PubMed

Publication Types

Grant support